Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-26T07:58:04.230Z Has data issue: false hasContentIssue false

Chimeric antigen receptor engineered T cells and their application in the immunotherapy of solid tumours

Published online by Cambridge University Press:  28 January 2022

Rui Mao
Affiliation:
Georgia Cancer Center, Augusta, USA
Mohamed S. Hussein
Affiliation:
Georgia Cancer Center, Augusta, USA
Yukai He*
Affiliation:
Georgia Cancer Center, Augusta, USA Department of Medicine, Medical College of Georgia, Augusta University, Augusta, USA
*
Author for correspondence: Yukai He, E-mail: [email protected]

Abstract

In this article, we reviewed the current literature studies and our understanding of the parameters that affect the chimeric antigen receptor T cells (CAR-T's) activation, effector function, in vivo persistence, and antitumour effects. These factors include T cell subsets and their differentiation stages, the components of chimeric antigen receptors (CAR) design, the expression promoters and delivery vectors, and the CAR-T production process. The CAR signalling and CAR-T activation were also studied in comparison to TCR. The last section of the review gave special consideration of CAR design for solid tumours, focusing on strategies to improve CAR-T tumour infiltration and survival in the hostile tumour microenvironment. With several hundred clinical trials undergoing worldwide, the pace of CAR-T immunotherapy moves from bench to bedside is unprecedented. We hope that the article will provide readers a clear and comprehensive view of this rapidly evolving field and will help scientists and physician to design effective CAR-Ts immunotherapy for solid tumours.

Type
Review
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Tumeh, PC et al. (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568571.CrossRefGoogle ScholarPubMed
Docta, RY et al. (2019) Tuning T-cell receptor affinity to optimize clinical risk-benefit when targeting alpha-fetoprotein-positive liver cancer. Hepatology 69, 20612075.CrossRefGoogle ScholarPubMed
Zhu, W et al. (2018) Identification of alpha-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immunotherapy. Hepatology 68, 574589.CrossRefGoogle ScholarPubMed
June, CH and Sadelain, M (2018) Chimeric antigen receptor therapy. New England Journal of Medicine 379, 6473.CrossRefGoogle ScholarPubMed
Rosenberg, SA et al. (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nature Reviews Cancer 8, 299308.CrossRefGoogle ScholarPubMed
Garber, K (2018) Driving T-cell immunotherapy to solid tumors. Nature Biotechnology 36, 215219.CrossRefGoogle ScholarPubMed
Manfredi, F et al. (2020) TCR Redirected T cells for cancer treatment: achievements, hurdles, and goals. Frontiers in Immunology 11, 1689. doi: 10.3389/fimmu.2020.01689.CrossRefGoogle ScholarPubMed
Zhao, Q et al. (2021) Engineered TCR-T cell immunotherapy in anticancer precision medicine: pros and cons. Frontiers in Immunology 12, 658753. doi: 10.3389/fimmu.2021.658753.CrossRefGoogle ScholarPubMed
Newick, K et al. (2017) CAR T cell therapy for solid tumors. Annual Review of Medicine 68, 139152.CrossRefGoogle ScholarPubMed
Miliotou, AN and Papadopoulou, LC (2018) CAR T-cell therapy: a New Era in cancer immunotherapy. Current Pharmaceutical Biotechnology 19, 518.CrossRefGoogle ScholarPubMed
June, CH et al. (2018) CAR T cell immunotherapy for human cancer. Science (New York, N.Y.) 359, 13611365.CrossRefGoogle Scholar
Depil, S et al. (2020) 'Off-the-shelf' allogeneic CAR T cells: development and challenges. Nature Reviews. Drug Discovery 19, 185199.CrossRefGoogle Scholar
Kim, DW and Cho, JY (2020) Recent advances in allogeneic CAR-T cells. Biomolecules 10, 263. doi: 10.3390/biom10020263.CrossRefGoogle ScholarPubMed
Farhood, B, Najafi, M and Mortezaee, K (2019) CD8(+) Cytotoxic T lymphocytes in cancer immunotherapy: a review. Journal of Cellular Physiology 234, 85098521.CrossRefGoogle ScholarPubMed
Borst, J et al. (2018) CD4( + ) T cell help in cancer immunology and immunotherapy. Nature Reviews Immunology 18, 635647.CrossRefGoogle ScholarPubMed
Yang, Y et al. (2017) TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance. Science Translational Medicine 9, eaag1209. doi: 10.1126/scitranslmed.aag1209.CrossRefGoogle ScholarPubMed
Wang, D et al. (2018) Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity. JCI Insight 3, e99048. doi: 10.1172/jci.insight.99048.CrossRefGoogle Scholar
Turtle, CJ et al. (2016) CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. Journal of Clinical Investigation 126, 21232138.CrossRefGoogle ScholarPubMed
Sommermeyer, D et al. (2016) Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia 30, 492500.CrossRefGoogle ScholarPubMed
Agarwal, S et al. (2020) In vivo generation of CAR T cells selectively in human CD4(+) lymphocytes. Molecular Therapy 28, 17831794.CrossRefGoogle Scholar
Jayaraman, J et al. (2020) CAR-T design: elements and their synergistic function. EBioMedicine 58, 102931.CrossRefGoogle ScholarPubMed
Restifo, NP and Gattinoni, L (2013) Lineage relationship of effector and memory T cells. Current Opinion in Immunology 25, 556563.CrossRefGoogle ScholarPubMed
Klebanoff, CA et al. (2005) Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proceedings of the National Academy of Sciences of the USA 102, 95719576.CrossRefGoogle ScholarPubMed
Hinrichs, CS et al. (2009) Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proceedings of the National Academy of Sciences of the USA 106, 1746917474.CrossRefGoogle ScholarPubMed
Berger, C et al. (2008) Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. Journal of Clinical Investigation 118, 294305.CrossRefGoogle ScholarPubMed
McLellan, AD and Ali Hosseini Rad, SM (2019) Chimeric antigen receptor T cell persistence and memory cell formation. Immunology and Cell Biology 97, 664674.CrossRefGoogle ScholarPubMed
Busch, DH et al. (2016) Role of memory T cell subsets for adoptive immunotherapy. Seminars in Immunology 28, 2834.CrossRefGoogle ScholarPubMed
Sadelain, M, Riviere, I and Riddell, S (2017) Therapeutic T cell engineering. Nature 545, 423431.CrossRefGoogle ScholarPubMed
Bailey, SR et al. (2017) Human CD26(high) T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence. Nature Communications 8, 1961.CrossRefGoogle ScholarPubMed
Nelson, MH et al. (2020) Identification of human CD4(+) T cell populations with distinct antitumor activity. Science Advances 6, eaba7443. doi: 10.1126/sciadv.aba7443.CrossRefGoogle ScholarPubMed
Wei, J et al. (2019) Target selection for CAR-T therapy. Journal of Hematology & Oncology 12, 62.CrossRefGoogle ScholarPubMed
Hill, JA et al. (2019) CAR-T – and a side order of IgG, to go? – immunoglobulin replacement in patients receiving CAR-T cell therapy. Blood Reviews 38, 100596.CrossRefGoogle Scholar
Paszkiewicz, PJ et al. (2016) Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. Journal of Clinical Investigation 126, 42624272.CrossRefGoogle Scholar
Shalabi, H et al. (2018) Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica 103, e215ee18.CrossRefGoogle ScholarPubMed
Majzner, RG and Mackall, CL (2018) Tumor antigen Escape from CAR T-cell therapy. Cancer Discovery 8, 12191226.CrossRefGoogle ScholarPubMed
Grupp, SA et al. (2018) Updated analysis of the efficacy and safety of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory (r/r) acute lymphoblastic leukemia. Blood 132(Supplement 1), 895895.CrossRefGoogle Scholar
Oak, J et al. (2018) Target antigen downregulation and other mechanisms of failure after axicabtagene ciloleucel (CAR19) therapy. Blood 132(Supplement 1), 46564656.CrossRefGoogle Scholar
Haso, W et al. (2013) Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 121, 11651174.CrossRefGoogle ScholarPubMed
Ruella, M et al. (2016) Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. Journal of Clinical Investigation 126, 38143826.CrossRefGoogle ScholarPubMed
Fry, TJ et al. (2018) CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature Medicine 24, 2028.CrossRefGoogle ScholarPubMed
Huang, L et al. (2017) Sequential infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T cells for adult patients with refractory/relapsed B-cell acute lymphoblastic leukemia. Blood 130, 846846.CrossRefGoogle Scholar
Gardner, R et al. (2018) Early clinical experience of CD19 x CD22 dual specific CAR T cells for enhanced anti-leukemic targeting of acute lymphoblastic leukemia. Blood 132(Supplement 1), 278278.CrossRefGoogle Scholar
Majzner, RG et al. (2020) Tuning the antigen density requirement for CAR T-cell activity. Cancer Discovery 10, 702723.CrossRefGoogle ScholarPubMed
Watanabe, K et al. (2015) Target antigen density governs the efficacy of anti-CD20-CD28-CD3 zeta chimeric antigen receptor-modified effector CD8+ T cells. Journal of Immunology 194, 911920.CrossRefGoogle ScholarPubMed
Ramakrishna, S et al. (2019) Modulation of target antigen density improves CAR T-cell functionality and persistence. Clinical Cancer Research 25, 53295341.CrossRefGoogle ScholarPubMed
Caruso, HG et al. (2015) Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Research 75, 35053518.CrossRefGoogle ScholarPubMed
Walker, AJ et al. (2017) Tumor antigen and receptor densities regulate efficacy of a chimeric antigen receptor targeting anaplastic lymphoma kinase. Molecular Therapy 25, 21892201.CrossRefGoogle ScholarPubMed
Srivastava, S and Riddell, SR (2015) Engineering CAR-T cells: design concepts. Trends in Immunology 36, 494502.CrossRefGoogle ScholarPubMed
Zhang, Z et al. (2019) Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor. Cell death & disease 10, 476.CrossRefGoogle Scholar
Godwin, CD et al. (2021) Targeting the membrane-proximal C2-set domain of CD33 for improved CD33-directed immunotherapy. Leukemia 35, 24962507.CrossRefGoogle ScholarPubMed
Velasco-Hernandez, T et al. (2020) Efficient elimination of primary B-ALL cells in vitro and in vivo using a novel 4-1BB-based CAR targeting a membrane-distal CD22 epitope. Journal for Immunotherapy of Cancer 8, e000896. doi: 10.1136/jitc-2020- 000896.CrossRefGoogle ScholarPubMed
Han, X et al. (2017) Adnectin-Based design of chimeric antigen receptor for T cell engineering. Molecular Therapy 25, 24662476.CrossRefGoogle ScholarPubMed
Hammill, JA et al. (2015) Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors. Journal for Immunotherapy of Cancer 3, 55.CrossRefGoogle ScholarPubMed
Xie, YJ et al. (2019) Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proceedings of the National Academy of Sciences of the USA 116, 76247631.CrossRefGoogle Scholar
Ahmad, ZA et al. (2012) scFv antibody: principles and clinical application. Clinical & Developmental Immunology 2012, 980250.CrossRefGoogle ScholarPubMed
Rafiq, S, Hackett, CS and Brentjens, RJ (2020) Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nature reviews. Clinical oncology 17, 147167.CrossRefGoogle ScholarPubMed
Guedan, S et al. (2019) Engineering and design of chimeric antigen receptors. Molecular Therapy. Methods & Clinical Development 12, 145156.CrossRefGoogle ScholarPubMed
Riano-Umbarila, L et al. (2020) Comparative assessment of the VH-VL and VL-VH orientations of single-chain variable fragments of scorpion toxin-neutralizing antibodies. Molecular Immunology 122, 141147.CrossRefGoogle ScholarPubMed
Cheng, Y et al. (2016) A VL-linker-VH orientation-dependent single-chain variable antibody fragment against rabies virus G protein with enhanced neutralizing potency in vivo. Protein and Peptide Letters 23, 2432.CrossRefGoogle ScholarPubMed
Gorovits, B and Koren, E (2019) Immunogenicity of chimeric antigen receptor T-cell therapeutics. BioDrugs 33, 275284.CrossRefGoogle ScholarPubMed
Zhao, Y et al. (2019) Treatment with humanized selective CD19CAR-T cells shows efficacy in highly treated B-ALL patients who have relapsed after receiving murine-based CD19CAR-T therapies. Clinical Cancer Research 25, 55955607.CrossRefGoogle ScholarPubMed
Sommermeyer, D et al. (2017) Fully human CD19-specific chimeric antigen receptors for T-cell therapy. Leukemia 31, 21912199.CrossRefGoogle ScholarPubMed
Stoiber, S et al. (2019) Limitations in the design of chimeric antigen receptors for cancer therapy. Cells 8, 472. doi: 10.3390/cells8050472.CrossRefGoogle ScholarPubMed
Singh, N et al. (2021) Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nature Medicine 27, 842850.CrossRefGoogle ScholarPubMed
Long, AH et al. (2015) 4-1BB Costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nature Medicine 21, 581590.CrossRefGoogle ScholarPubMed
Hege, K (2021) Context matters in CAR T cell tonic signaling. Nature Medicine 27, 763764.CrossRefGoogle Scholar
Lynn, RC et al. (2016) High-affinity FRbeta-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity. Leukemia 30, 13551364.CrossRefGoogle Scholar
Richman, SA et al. (2018) High-Affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunology Research 6, 3646.CrossRefGoogle Scholar
Hudecek, M et al. (2013) Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells. Clinical Cancer Research 19, 31533164.CrossRefGoogle ScholarPubMed
Chmielewski, M et al. (2004) T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity. Journal of Immunology 173, 76477653.CrossRefGoogle Scholar
Oren, R et al. (2014) Functional comparison of engineered T cells carrying a native TCR versus TCR-like antibody-based chimeric antigen receptors indicates affinity/avidity thresholds. Journal of Immunology 193, 57335743.CrossRefGoogle ScholarPubMed
Ghorashian, S et al. (2019) Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nature Medicine 25, 14081414.CrossRefGoogle Scholar
Drent, E et al. (2017) A rational strategy for reducing on-target Off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Molecular Therapy 25, 19461958.CrossRefGoogle ScholarPubMed
Greenman, R et al. (2021) Shaping functional avidity of CAR T cells: affinity, avidity, and antigen density that regulate response. Molecular Cancer Therapeutics 20, 872884.CrossRefGoogle Scholar
Weber, EW et al. (2021) Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science (New York, N.Y.) 372, eaba1786. doi: 10.1126/science.aba1786.CrossRefGoogle ScholarPubMed
Caraballo Galva, LD et al. (2021) Novel low-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC. Hepatology, doi: 10.1002/hep.32279.CrossRefGoogle Scholar
Xu-Monette, ZY et al. (2017) PD-1/PD-L1 blockade: have We found the Key to unleash the antitumor immune response? Frontiers in Immunology 8, 1597.CrossRefGoogle ScholarPubMed
Hudecek, M et al. (2015) The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunology Research 3, 125135.CrossRefGoogle ScholarPubMed
Guest, RD et al. (2005) The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens. Journal of Immunotherapy 28, 203211.CrossRefGoogle ScholarPubMed
Wilkie, S et al. (2008) Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. Journal of Immunology 180, 49014909.CrossRefGoogle Scholar
Alabanza, L et al. (2017) Function of novel anti-CD19 chimeric antigen receptors with human variable regions Is affected by hinge and transmembrane domains. Molecular Therapy 25, 24522465.CrossRefGoogle ScholarPubMed
Fujiwara, K et al. (2020) Hinge and transmembrane domains of chimeric antigen receptor regulate receptor expression and signaling threshold. Cells 9, 1182. doi: 10.3390/cells9051182.CrossRefGoogle ScholarPubMed
Ying, Z et al. (2019) A safe and potent anti-CD19 CAR T cell therapy. Nature Medicine 25, 947953.CrossRefGoogle ScholarPubMed
Savoldo, B et al. (2011) CD28 Costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. Journal of Clinical Investigation 121, 18221826.CrossRefGoogle ScholarPubMed
Muller, YD et al. (2021) The CD28-transmembrane domain mediates chimeric antigen receptor heterodimerization With CD28. Frontiers in Immunology 12, 639818.CrossRefGoogle ScholarPubMed
Guedan, S et al. (2018) Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation. JCI Insight 3, e96976. doi: 10.1172/jci.insight.96976.CrossRefGoogle Scholar
Kuwana, Y et al. (1987) Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions. Biochemical and Biophysical Research Communications 149, 960968.CrossRefGoogle ScholarPubMed
Gross, G, Waks, T and Eshhar, Z (1989) Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proceedings of the National Academy of Sciences of the USA 86, 10024–8.CrossRefGoogle ScholarPubMed
Eshhar, Z et al. (1993) Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proceedings of the National Academy of Sciences 90, 720724.CrossRefGoogle ScholarPubMed
Sadelain, M, Riviere, I and Brentjens, R (2003) Targeting tumours with genetically enhanced T lymphocytes. Nature Reviews Cancer 3, 3545.CrossRefGoogle ScholarPubMed
Finney, HM et al. (1998) Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. Journal of Immunology 161, 27912797.Google Scholar
Finney, HM, Akbar, AN and Lawson, AD (2004) Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. Journal of Immunology 172, 104113.CrossRefGoogle ScholarPubMed
Weinkove, R et al. (2019) Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations. Clinical & Translational Immunology 8, e1049.CrossRefGoogle ScholarPubMed
Drent, E et al. (2019) Combined CD28 and 4-1BB costimulation potentiates affinity-tuned chimeric antigen receptor-engineered T cells. Clinical Cancer Research 25, 40144025.CrossRefGoogle ScholarPubMed
Zhao, Z et al. (2015) Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. Cancer Cell 28, 415428.CrossRefGoogle ScholarPubMed
Maude, SL et al. (2018) Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine 378, 439448.CrossRefGoogle Scholar
Kawalekar, OU et al. (2016) Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity 44, 380390.CrossRefGoogle ScholarPubMed
Parry, RV et al. (2003) CD28 And inducible costimulatory protein Src homology 2 binding domains show distinct regulation of phosphatidylinositol 3-kinase, Bcl-xL, and IL-2 expression in primary human CD4 T lymphocytes. Journal of Immunology 171, 166174.CrossRefGoogle ScholarPubMed
Fos, C et al. (2008) ICOS Ligation recruits the p50alpha PI3 K regulatory subunit to the immunological synapse. Journal of Immunology 181, 19691977.CrossRefGoogle Scholar
Croft, M et al. (2009) The significance of OX40 and OX40L to T-cell biology and immune disease. Immunological Reviews 229, 173191.CrossRefGoogle ScholarPubMed
Zhang, H et al. (2021) A chimeric antigen receptor with antigen-independent OX40 signaling mediates potent antitumor activity. Science translational medicine 13, eaba7308. doi: 10.1126/scitranslmed.aba7308.CrossRefGoogle ScholarPubMed
Guercio, M et al. (2021) CD28.OX40 co-stimulatory combination is associated with long in vivo persistence and high activity of CAR.CD30 T-cells. Haematologica 106, 987999.CrossRefGoogle ScholarPubMed
Hombach, AA and Abken, H (2011) Costimulation by chimeric antigen receptors revisited the T cell antitumor response benefits from combined CD28-OX40 signalling. International Journal of Cancer 129, 29352944.CrossRefGoogle Scholar
Song, DG et al. (2012) CD27 Costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood 119, 696706.CrossRefGoogle ScholarPubMed
Chen, H et al. (2021) CD27 Enhances the killing effect of CAR T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors. Cancer Immunology Immunotherapy 70, 20592071.CrossRefGoogle Scholar
Wang, D et al. (2019) Abstract 2321: dual-function of CD27-CD70 costimulatory signal in CAR T cell therapy. Cancer Research 79(13 Supplement), 23212321.Google Scholar
Flemming, A (2020) CD3epsilon Tunes CAR T cell anticancer activity. Nature Reviews Immunology 20, 520521.CrossRefGoogle Scholar
Wu, W et al. (2020) Multiple signaling roles of CD3epsilon and Its application in CAR-T cell therapy. Cell 182, 855871, e23.CrossRefGoogle ScholarPubMed
Brentjens, RJ et al. (2011) Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118, 48174828.CrossRefGoogle ScholarPubMed
Noaks, E et al. (2021) Enriching leukapheresis improves T cell activation and transduction efficiency during CAR T processing. Molecular Therapy. Methods & Clinical Development 20, 675687.CrossRefGoogle Scholar
D'Aloia, MM et al. (2018) CAR-T cells: the long and winding road to solid tumors. Cell death & disease 9, 282.CrossRefGoogle Scholar
Eyquem, J et al. (2017) Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543, 113117.CrossRefGoogle Scholar
Frigault, MJ et al. (2015) Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells. Cancer Immunology Research 3, 356367.CrossRefGoogle ScholarPubMed
Gomes-Silva, D et al. (2017) Tonic 4-1BB costimulation in chimeric antigen receptors impedes T cell survival and Is vector-dependent. Cell Reports 21, 1726.CrossRefGoogle ScholarPubMed
Rad, SMA et al. (2020) Promoter choice: who should drive the CAR in T cells? PLoS One 15, e0232915.CrossRefGoogle Scholar
Ho, JY et al. (2021) Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cells in vivo. Molecular Therapy. Methods & Clinical Development 21, 237246.CrossRefGoogle ScholarPubMed
Stock, S, Schmitt, M and Sellner, L (2019) Optimizing manufacturing protocols of chimeric antigen receptor T cells for improved anticancer immunotherapy. International journal of molecular sciences 20, 6223. doi: 10.3390/ijms20246223.CrossRefGoogle ScholarPubMed
Kalamasz, D et al. (2004) Optimization of human T-cell expansion ex vivo using magnetic beads conjugated with anti-CD3 and anti-CD28 antibodies. Journal of Immunotherapy 27, 405418.CrossRefGoogle ScholarPubMed
Zhou, J et al. (2019) Chimeric antigen receptor T (CAR-T) cells expanded with IL-7/IL-15 mediate superior antitumor effects. Protein & Cell 10, 764769.CrossRefGoogle Scholar
Xu, Y et al. (2014) Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19–T cells and are preserved by IL-7 and IL-15. Blood 123, 37503759.CrossRefGoogle ScholarPubMed
Quintarelli, C et al. (2018) Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma. OncoImmunology 7, e1433518.CrossRefGoogle ScholarPubMed
Gargett, T and Brown, MP (2015) Different cytokine and stimulation conditions influence the expansion and immune phenotype of third-generation chimeric antigen receptor T cells specific for tumor antigen GD2. Cytotherapy 17, 487495.CrossRefGoogle ScholarPubMed
Ptáčková, P et al. (2018) A new approach to CAR T-cell gene engineering and cultivation using piggyBac transposon in the presence of IL-4, IL-7 and IL-21. Cytotherapy 20, 507520.CrossRefGoogle ScholarPubMed
Wu, L et al. (2020) Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells. Cellular & Molecular Immunology 17, 600612.CrossRefGoogle Scholar
Lindner, SE et al. (2020) Chimeric antigen receptor signaling: functional consequences and design implications. Science Advances 6, eaaz3223.CrossRefGoogle ScholarPubMed
Courtney, AH, Lo, W-L and Weiss, A (2018) TCR Signaling: mechanisms of initiation and propagation. Trends in Biochemical Sciences 43, 108123.CrossRefGoogle Scholar
Hwang, J-R et al. (2020) Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development. Experimental & Molecular Medicine 52, 750761.CrossRefGoogle Scholar
Salter, AI et al. (2018) Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function. Science Signaling 11, eaat6753. doi: 10.1126/scisignal.aat6753.CrossRefGoogle ScholarPubMed
Brameshuber, M et al. (2018) Monomeric TCRs drive T cell antigen recognition. Nature Immunology 19, 487496.CrossRefGoogle ScholarPubMed
Chang, ZL et al. (2018) Rewiring T-cell responses to soluble factors with chimeric antigen receptors. Nature Chemical Biology 14, 317324.CrossRefGoogle ScholarPubMed
Davenport, AJ et al. (2018) Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity. Proceedings of the National Academy of Sciences 115, E2068E2E76.CrossRefGoogle ScholarPubMed
Karlsson, H et al. (2015) Evaluation of intracellular signaling downstream chimeric antigen receptors. PLoS One 10, e0144787.CrossRefGoogle ScholarPubMed
Ramello, MC et al. (2019) An immunoproteomic approach to characterize the CAR interactome and signalosome. Science Signaling 12, eaap9777. doi: 10.1126/scisignal.aap9777.CrossRefGoogle ScholarPubMed
Benmebarek, MR et al. (2019) Killing mechanisms of Chimeric Antigen Receptor (CAR) T cells. International journal of molecular sciences 20, 1283. doi: 10.3390/ijms20061283.CrossRefGoogle ScholarPubMed
Voskoboinik, I, Smyth, MJ and Trapani, JA (2006) Perforin-mediated target-cell death and immune homeostasis. Nature Reviews Immunology 6, 940952.CrossRefGoogle ScholarPubMed
Meiraz, A et al. (2009) Switch from perforin-expressing to perforin-deficient CD8(+) T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo. Immunology 128, 6982.CrossRefGoogle Scholar
Upadhyay, R et al. (2021) A critical role for Fas-mediated Off-target tumor killing in T-cell immunotherapy. Cancer Discovery 11, 599613.CrossRefGoogle ScholarPubMed
Siegel, RM et al. (2000) The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nature Immunology 1, 469474.CrossRefGoogle ScholarPubMed
Tschumi, BO et al. (2018) CART Cells are prone to Fas- and DR5-mediated cell death. Journal for Immunotherapy of Cancer 6, 71.CrossRefGoogle ScholarPubMed
Yamamoto, TN et al. (2019) T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy. Journal of Clinical Investigation 129, 15511565.CrossRefGoogle ScholarPubMed
Zhang, B et al. (2008) IFN-gamma- and TNF-dependent bystander eradication of antigen-loss variants in established mouse cancers. Journal of Clinical Investigation 118, 13981404.CrossRefGoogle ScholarPubMed
Landsberg, J et al. (2012) Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature 490, 412416.CrossRefGoogle ScholarPubMed
Bertrand, F et al. (2015) Blocking tumor necrosis factor-alpha enhances CD8 T-cell-dependent immunity in experimental melanoma. Cancer Research 75, 26192628.CrossRefGoogle ScholarPubMed
Torrey, H et al. (2017) Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs. Science Signaling 10, eaaf8608. doi: 10.1126/scisignal.aaf8608.CrossRefGoogle ScholarPubMed
Le Poole, IC et al. (2002) Interferon-gamma reduces melanosomal antigen expression and recognition of melanoma cells by cytotoxic T cells. American Journal of Pathology 160, 521528.CrossRefGoogle ScholarPubMed
Montfort, A et al. (2019) The TNF paradox in cancer progression and immunotherapy. Frontiers in Immunology 10, 1818.CrossRefGoogle ScholarPubMed
Jorgovanovic, D et al. (2020) Roles of IFN-gamma in tumor progression and regression: a review. Biomarker Research 8, 49.CrossRefGoogle ScholarPubMed
Pule, MA et al. (2008) Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nature Medicine 14, 12641270.CrossRefGoogle ScholarPubMed
Pulè, MA et al. (2005) A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Molecular Therapy 12, 933941.CrossRefGoogle ScholarPubMed
Rossig, C et al. (2002) Epstein-Barr virus–specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy. Blood 99, 20092016.CrossRefGoogle Scholar
Aamir, S et al. (2021) Systematic review and meta-analysis of CD19-specific CAR-T cell therapy in relapsed/refractory acute lymphoblastic leukemia in the pediatric and young adult population: safety and efficacy outcomes. Clinical Lymphoma Myeloma and Leukemia 21, e334ee47.CrossRefGoogle Scholar
Hou, B et al. (2019) Efficiency of CAR-T therapy for treatment of solid tumor in clinical trials: a meta-analysis. Disease Markers 2019, 3425291.CrossRefGoogle ScholarPubMed
Schaft, N (2020) The landscape of CAR-T cell clinical trials against solid tumors-A comprehensive overview. Cancers (Basel) 12, 2567. doi: 10.3390/cancers12092567.CrossRefGoogle ScholarPubMed
Gu, R et al. (2020) Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia. Journal of Hematology & Oncology 13, 122.CrossRefGoogle ScholarPubMed
Bielamowicz, K et al. (2018) Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma. Neuro-Oncology 20, 506518.CrossRefGoogle Scholar
Hurton, LV et al. (2016) Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proceedings of the National Academy of Sciences of the USA 113, E7788E7E97.CrossRefGoogle ScholarPubMed
Chmielewski, M and Abken, H (2015) TRUCKs: the fourth generation of CARs. Expert Opinion on Biological Therapy 15, 11451154.CrossRefGoogle ScholarPubMed
Caraballo Galva, LD et al. (2020) Engineering T cells for immunotherapy of primary human hepatocellular carcinoma. Journal of Genetics and Genomics 47, 115.CrossRefGoogle ScholarPubMed
Jin, J et al. (2020) Fueling chimeric antigen receptor T cells with cytokines. American Journal of Cancer Research 10, 40384055.Google ScholarPubMed
Chmielewski, M, Hombach, AA and Abken, H (2014) Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunological Reviews 257, 8390.CrossRefGoogle ScholarPubMed
Di Stasi, A et al. (2009) T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 113, 63926402.CrossRefGoogle Scholar
Kagoya, Y et al. (2018) A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nature Medicine 24, 352359.CrossRefGoogle ScholarPubMed
Johnson, LR et al. (2021) The immunostimulatory RNA RN7SL1 enables CAR-T cells to enhance autonomous and endogenous immune function. Cell 184, 49814995, e14.CrossRefGoogle ScholarPubMed
Baeuerle, PA et al. (2019) Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response. Nature Communications 10, 2087.CrossRefGoogle ScholarPubMed
Xu, Y et al. (2018) A novel antibody-TCR (AbTCR) platform combines Fab-based antigen recognition with gamma/delta-TCR signaling to facilitate T-cell cytotoxicity with low cytokine release. Cell Discovery 4, 62.CrossRefGoogle ScholarPubMed
Helsen, CW et al. (2018) The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity. Nature Communications 9, 3049.CrossRefGoogle Scholar
Liu, Y et al. (2021) Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors. Science Translational Medicine 13, eabb5191. doi: 10.1126/scitranslmed.abb5191.CrossRefGoogle ScholarPubMed
Donnadieu, E et al. (2020) Surmounting the obstacles that impede effective CAR T cell trafficking to solid tumors. Journal of Leukocyte Biology 108, 10671079.CrossRefGoogle Scholar
Hou, AJ, Chen, LC and Chen, YY (2021) Navigating CAR-T cells through the solid-tumour microenvironment. Nature Reviews Drug Discovery 20, 531550.CrossRefGoogle ScholarPubMed
Martinez, M and Moon, EK (2019) CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Frontiers in Immunology 10, 128.CrossRefGoogle Scholar
Tian, Y et al. (2020) Gene modification strategies for next-generation CAR T cells against solid cancers. Journal of Hematology & Oncology 13, 54.CrossRefGoogle Scholar
Scarfo, I and Maus, MV (2017) Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment. Journal for Immunotherapy of Cancer 5, 28.CrossRefGoogle Scholar
Pocaterra, A, Catucci, M and Mondino, A (2022) Adoptive T cell therapy of solid tumors: time to team up with immunogenic chemo/radiotherapy. Current Opinion in Immunology 74, 5359.CrossRefGoogle Scholar
Xu, J et al. (2018) Combination therapy: a feasibility strategy for CAR-T cell therapy in the treatment of solid tumors. Oncology Letters 16, 20632070.Google ScholarPubMed
Murad, JP et al. (2021) Pre-conditioning modifies the TME to enhance solid tumor CAR T cell efficacy and endogenous protective immunity. Molecular Therapy 29, 23352349.CrossRefGoogle Scholar
Jin, L et al. (2019) CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nature Communications 10, 4016.CrossRefGoogle ScholarPubMed
Caruana, I et al. (2015) Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nature Medicine 21, 524529.CrossRefGoogle ScholarPubMed
Ford, K et al. (2020) NOX4 Inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumors. Cancer Research 80, 18461860.CrossRefGoogle ScholarPubMed
Adachi, K et al. (2018) IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nature Biotechnology 36, 346351.CrossRefGoogle ScholarPubMed
Craddock, JA et al. (2010) Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. Journal of Immunotherapy 33, 780788.CrossRefGoogle ScholarPubMed
Whilding, LM et al. (2019) CAR T-cells targeting the integrin alphavbeta6 and co-expressing the chemokine receptor CXCR2 demonstrate enhanced homing and efficacy against several solid malignancies. Cancers (Basel) 11, 674. doi: 10.3390/cancers11050674.CrossRefGoogle ScholarPubMed
Dangaj, D et al. (2019) Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors. Cancer Cell 35, 885900, e10.CrossRefGoogle ScholarPubMed
Feig, C et al. (2013) Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proceedings of the National Academy of Sciences of the USA 110, 20212–7.CrossRefGoogle ScholarPubMed
Tay, RE, Richardson, EK and Toh, HC (2021) Revisiting the role of CD4(+) T cells in cancer immunotherapy-new insights into old paradigms. Cancer Gene Therapy 28, 517.CrossRefGoogle ScholarPubMed
Leen, AM et al. (2014) Reversal of tumor immune inhibition using a chimeric cytokine receptor. Molecular Therapy 22, 12111220.CrossRefGoogle ScholarPubMed
Wang, Y et al. (2019) An IL-4/21 inverted cytokine receptor improving CAR-T cell potency in immunosuppressive solid-tumor microenvironment. Frontiers in Immunology 10, 1691.CrossRefGoogle ScholarPubMed
Datta, M et al. (2019) Reprogramming the tumor microenvironment to improve immunotherapy: emerging strategies and combination therapies. American Society of Clinical Oncology Educational Book / Asco. American Society of Clinical Oncology. Meeting 39, 165174.CrossRefGoogle ScholarPubMed
Chang, ZL, Hou, AJ and Chen, YY (2020) Engineering primary T cells with chimeric antigen receptors for rewired responses to soluble ligands. Nature Protocols 15, 15071524.CrossRefGoogle ScholarPubMed
Bollard, CM et al. (2002) Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood 99, 31793187.CrossRefGoogle ScholarPubMed
Cherkassky, L et al. (2016) Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. Journal of Clinical Investigation 126, 31303144.CrossRefGoogle Scholar
Rafiq, S et al. (2018) Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nature Biotechnology 36, 847856.CrossRefGoogle ScholarPubMed
Pegram, HJ et al. (2012) Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood 119, 41334141.CrossRefGoogle ScholarPubMed
Hu, B et al. (2017) Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18. Cell Reports 20, 30253033.CrossRefGoogle Scholar
Ma, X et al. (2020) Interleukin-23 engineering improves CAR T cell function in solid tumors. Nature Biotechnology 38, 448459.CrossRefGoogle Scholar
Buchan, SL et al. (2018) Antibodies to costimulatory receptor 4-1BB enhance anti-tumor immunity via T regulatory cell depletion and promotion of CD8 T cell effector function. Immunity 49, 958970, e7.CrossRefGoogle Scholar
Nakagawa, H et al. (2016) Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity. Proceedings of the National Academy of Sciences of the USA 113, 62486253.CrossRefGoogle ScholarPubMed
Overacre-Delgoffe, AE et al. (2017) Interferon-γ drives treg fragility to promote anti-tumor immunity. Cell 169, 11301141, e11.CrossRefGoogle ScholarPubMed
Beatty, GL et al. (2011) CD40 Agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science (New York, N.Y.) 331, 16121616.CrossRefGoogle ScholarPubMed
Petty, AJ et al. (2021) Targeting tumor-associated macrophages in cancer immunotherapy. Cancers 13, 5318.CrossRefGoogle ScholarPubMed
Bocca, P et al. (2017) Bevacizumab-mediated tumor vasculature remodelling improves tumor infiltration and antitumor efficacy of GD2-CAR T cells in a human neuroblastoma preclinical model. Oncoimmunology 7, e1378843.CrossRefGoogle Scholar
Bader, JE, Voss, K and Rathmell, JC (2020) Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy. Molecular Cell 78, 10191033.CrossRefGoogle ScholarPubMed
Valkenburg, KC, de Groot, AE and Pienta, KJ (2018) Targeting the tumour stroma to improve cancer therapy. Nature Reviews. Clinical Oncology 15, 366381.CrossRefGoogle ScholarPubMed
Yu, S et al. (2019) Next-generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Molecular Cancer 18, 125.CrossRefGoogle ScholarPubMed
Roybal, KT et al. (2016) Engineering T cells with customized therapeutic response programs using synthetic notch receptors. Cell 167, 419432, e16.CrossRefGoogle ScholarPubMed
Morsut, L et al. (2016) Engineering customized cell sensing and response behaviors using synthetic notch receptors. Cell 164, 780791.CrossRefGoogle ScholarPubMed
Choe, JH et al. (2021) SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Science translational medicine 13, eabe7378. doi: 10.1126/scitranslmed.abe7378.CrossRefGoogle ScholarPubMed
Hyrenius-Wittsten, A et al. (2021) SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models. Science translational medicine 13, eabd8836. doi: 10.1126/scitranslmed.abd8836.CrossRefGoogle ScholarPubMed
Lajoie, MJ et al. (2020) Designed protein logic to target cells with precise combinations of surface antigens. Science (New York, N.Y.) 369, 16371643.CrossRefGoogle ScholarPubMed
Klichinsky, M et al. (2020) Human chimeric antigen receptor macrophages for cancer immunotherapy. Nature Biotechnology 38, 947953.CrossRefGoogle ScholarPubMed
Molthoff, CF et al. (1992) Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen. Journal of Nuclear Medicine 33, 20002005.Google ScholarPubMed
Kershaw, MH, Westwood, JA and Hwu, P (2002) Dual-specific T cells combine proliferation and antitumor activity. Nature Biotechnology 20, 12211227.CrossRefGoogle ScholarPubMed
Kershaw, MH et al. (2006) A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clinical Cancer Research 12, 61066115.CrossRefGoogle ScholarPubMed
Cheung, NK et al. (2012) Humanizing murine IgG3 anti-GD2 antibody m3F8 substantially improves antibody-dependent cell-mediated cytotoxicity while retaining targeting in vivo. Oncoimmunology 1, 477486.CrossRefGoogle ScholarPubMed
Rossig, C et al. (2002) Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy. Blood 99, 20092016.CrossRefGoogle Scholar
Louis, CU et al. (2011) Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118, 60506056.CrossRefGoogle ScholarPubMed
Heczey, A et al. (2017) CAR T cells administered in combination with lymphodepletion and PD-1 inhibition to patients with neuroblastoma. Molecular Therapy 25, 22142224.CrossRefGoogle Scholar
Nakamura, K et al. (2001) Construction of humanized anti-ganglioside monoclonal antibodies with potent immune effector functions. Cancer Immunology Immunotherapy 50, 275284.CrossRefGoogle ScholarPubMed
Straathof, K et al. (2018) Abstract CT145: a cancer research UK phase I trial of anti-GD2 chimeric antigen receptor (CAR) transduced T-cells (1RG-CART) in patients with relapsed or refractory neuroblastoma. Cancer Research 78(13 Supplement), CT145CCT45.Google Scholar
Park, JR et al. (2007) Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Molecular Therapy 15, 825833.CrossRefGoogle ScholarPubMed
Akamatsu, Y et al. (1998) A single-chain immunotoxin against carcinoembryonic antigen that suppresses growth of colorectal carcinoma cells. Clinical Cancer Research 4, 28252832.Google ScholarPubMed
Katz, SC et al. (2015) Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor–modified T-cell therapy for CEA+ liver metastases. Clinical Cancer Research 21, 31493159.CrossRefGoogle ScholarPubMed
Rios, X et al. (2019) Immuno-PET imaging and pharmacokinetics of an anti-CEA scFv-based trimerbody and Its monomeric counterpart in human gastric carcinoma-bearing mice. Molecular Pharmaceutics 16, 10251035.CrossRefGoogle ScholarPubMed
Thistlethwaite, FC et al. (2017) The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity. Cancer Immunology, Immunotherapy 66, 14251436.CrossRefGoogle Scholar
Jiang, H et al. (2018) Claudin18.2-specific chimeric antigen receptor engineered T cells for the treatment of gastric cancer. JNCI: Journal of the National Cancer Institute 111, 409418.CrossRefGoogle Scholar
Zhan, X et al. (2019) Phase I trial of claudin 18.2-specific chimeric antigen receptor T cells for advanced gastric and pancreatic adenocarcinoma. Journal of Clinical Oncology 37(15_suppl), 25092509.CrossRefGoogle Scholar
Merchant, M et al. (2013) Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proceedings of the National Academy of Sciences of the USA 110, E2987E2996.CrossRefGoogle ScholarPubMed
Tchou, J et al. (2017) Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunology Research 5, 11521161.CrossRefGoogle ScholarPubMed
Nevoltris, D et al. (2015) Conformational nanobodies reveal tethered epidermal growth factor receptor involved in EGFR/ErbB2 predimers. ACS Nano 9, 13881399.CrossRefGoogle ScholarPubMed
Feng, K et al. (2016) Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Science China Life Sciences 59, 468479.CrossRefGoogle ScholarPubMed
Guo, Y et al. (2018) Phase I study of chimeric antigen receptor–modified T cells in patients with EGFR-positive advanced biliary tract cancers. Clinical Cancer Research 24, 12771286.CrossRefGoogle ScholarPubMed
Johnson, LA et al. (2015) Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Science Translational Medicine 7, 275ra22.CrossRefGoogle ScholarPubMed
O'Rourke, DM et al. (2017) A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Science Translational Medicine 9, eaaa0984.CrossRefGoogle Scholar
Shi, D et al. (2020) Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: results of phase I trials. Clinical Cancer Research 26, 39793989.CrossRefGoogle ScholarPubMed
Choi, J et al. (2019) Antigen-binding affinity and thermostability of chimeric mouse-chicken IgY and mouse-human IgG antibodies with identical variable domains. Scientific Reports 9, 19242.CrossRefGoogle ScholarPubMed
Junghans, RP et al. (2016) Phase I trial of anti-PSMA designer CAR-T cells in prostate cancer: possible role for interacting interleukin 2-T cell pharmacodynamics as a determinant of clinical response. The Prostate 76, 12571270.CrossRefGoogle ScholarPubMed
Choi, MY et al. (2015) Pre-clinical specificity and safety of UC-961, a first-In-class monoclonal antibody targeting ROR1. Clinical Lymphoma Myeloma and Leukemia 15, S167SS69.CrossRefGoogle ScholarPubMed
Specht, JM et al. (2018) Abstract CT131: a phase I study of adoptive immunotherapy for advanced ROR1+ malignancies with defined subsets of autologous T cells expressing a ROR1-specific chimeric antigen receptor (ROR1-CAR). Cancer Research 78(13 Supplement), CT131CCT31.Google Scholar