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25 - Adoptive cellular immunotherapy

from Section 3 - Evaluation and treatment

Published online by Cambridge University Press:  05 April 2013

By
Hyoung Jin Kang ,
Cliona M. Rooney  and
Helen E. Heslop
Edited by
Ching-Hon Pui
Ching-Hon Pui
Affiliation:
St Jude's Children's Research Hospital
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Summary

Introduction

The possibility that the immune system can be harnessed to play a role in eradicating leukemia has long been an attractive concept. Numerous experiments in animal models have convincingly shown that T-lymphocytes recognize and kill malignant cells. However, human immunotherapy with non-specific stimulants, such as BCG (Calmette–Guérin bacillus), has not had a successful history. Recently, improved knowledge of the molecular basis of antigen presentation and T-cell recognition of antigen has made it clear that tumors possess antigens that could be targets for activated T-cells. Interest in cellular immunotherapy has also been stimulated by clinical studies showing the efficacy of unmanipulated donor T-cells as therapy for relapse after allogeneic bone marrow transplantation (BMT). In this chapter we review clinical immunotherapy strategies now being applied in the treatment of leukemia.

Immune system recognition of tumor cells

Recent advances in basic immunology have provided important insights into the mechanisms by which the immune system recognizes tumor cells. Dissection of the processes of antigen presentation and T-cell recognition of antigen has yielded particularly useful information in this regard. Advances in genomics have also simplified the identification of putative tumor antigens through the use of new informatics tools to deduce epitopes from candidate genes.

Type
Chapter
Information
Childhood Leukemias , pp. 582 - 592
Publisher: Cambridge University Press
Print publication year: 2012

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References

Rosenberg, SA, Restifo, NP, Yang, JC, Morgan, RA, Dudley, ME.Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008;8:299–308.CrossRefGoogle ScholarPubMed
Kolb, HJ.Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 2008;112:4371–4383.CrossRefGoogle ScholarPubMed
Jensen, PE.Recent advances in antigen processing and presentation. Nat Immunol 2007;8:1041–1048.CrossRefGoogle ScholarPubMed
Adema, GJ.Dendritic cells from bench to bedside and back. Immunol Lett 2009;122:128–130.CrossRefGoogle Scholar
Levitskaya, J, Coram, M, Levitsky, V, et al. Inhibition of antigen processing by the internal repeat region of the Epstein–Barr virus nuclear antigen-1. Nature 1995;375:685–688.CrossRefGoogle ScholarPubMed
Androlewicz, M, Cresswell, P.How selective is the transporter associated with antigen processing?Immunity 1996;5:1–5.CrossRefGoogle ScholarPubMed
Levitsky, V, Zhang, Q-J, Levitskaya, J, Masucci, MG.The life span of major histocompatibility complex-peptide complexes influences the efficiency of presentation and immunogenicity of two class-I restricted cytotoxic T lymphocyte epitopes in the Epstein–Barr virus nuclear antigen 4. J Exp Med 1996;183:915–926.CrossRefGoogle Scholar
Viola, A, Lanzavecchia, A.T cell activation determined by T cell receptor number and tunable thresholds. Science 1996;273:104–106.CrossRefGoogle Scholar
Dao, T, Scheinberg, DA.Peptide vaccines for myeloid leukaemias. Best Pract Res Clin Haematol 2008;21:391–404.CrossRefGoogle ScholarPubMed
Cheever, MA, Allison, JP, Ferris, AS, The prioritization of cancer antigens: a National Cancer Institute pilot project for the acceleration of translational research. Clin Cancer Res 2009;15:5323–5337.CrossRefGoogle ScholarPubMed
Heslop, HE, Slobod, KS, Pulé, MA. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 2010;115:925–935.CrossRefGoogle ScholarPubMed
Bollard, CM, Gottschalk, S, Leen, AM, et al. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood 2007;110: 2838–2845.CrossRefGoogle ScholarPubMed
Vilchez, RA, Madden, CR, Kozinetz, CA, et al. Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 2002;359:817–823.CrossRefGoogle ScholarPubMed
Rezvani, K, Yong, AS, Mielke, S, et al. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood 2008;111:236–242.CrossRefGoogle ScholarPubMed
Popat, U, Carrum, G, May, R, et al. CD52 and CD45 monoclonal antibodies for reduced intensity hemopoietic stem cell transplantation from HLA matched and one antigen mismatched unrelated donors. Bone Marrow Transplant 2005;35:1127–1132.CrossRefGoogle ScholarPubMed
Micklethwaite, KP, Savoldo, B, Hanley, PJ, et al. Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation. Blood 2010;115:2695–2703.CrossRefGoogle Scholar
Jensen, MC, Popplewell, L, Cooper, LJ, et al. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor re-directed T cells in humans. Biol Blood Marrow Transplant 2010;16:1245–1256.CrossRefGoogle Scholar
Landmeier, S, Altvater, B, Pscherer, S, et al. Cytotoxic T cells transduced with chimeric anti-CD19 receptors prevent engraftment of primary lymphoblastic leukemia in vivo. Leukemia 2010;24:1080–1084.CrossRefGoogle ScholarPubMed
Stronen, E, Abrahamsen, IW, Gaudernack, G, et al. Dendritic cells engineered to express defined allo-HLA peptide complexes induce antigen-specific cytotoxic T cells efficiently killing tumour cells. Scand J Immunol 2009;69:319–328.CrossRefGoogle ScholarPubMed
Zendman, AJ, Ruiter, DJ, van Muijen, GN.Cancer/testis-associated genes: identification, expression profile, and putative function. J Cell Physiol 2003;194:272–288.CrossRefGoogle ScholarPubMed
Vonderheide, RH.Telomerase as a universal tumor-associated antigen for cancer immunotherapy. Oncogene 2002;21:674–679.CrossRefGoogle ScholarPubMed
Clark, RE, Dodi, IA, Hill, SC, et al. Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein. Blood 2001;98: 2887–2893.CrossRefGoogle ScholarPubMed
Schmitt, M, Schmitt, A, Rojewski, MT, et al. RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood 2008;111:1357–1365.CrossRefGoogle ScholarPubMed
Spaapen, R, Mutis, T.Targeting haematopoietic-specific minor histocompatibility antigens to distinguish graft-versus-tumour effects from graft-versus-host disease. Best Pract Res Clin Haematol 2008;21:543–557.CrossRefGoogle ScholarPubMed
Warren, EH, Fujii, N, Akatsuka, Y, et al. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplant with T cells specific for minor histocompatibility antigens. Blood 2010;115:3869–3878.CrossRefGoogle Scholar
Ambinder, RF.Epstein–Barr virus and Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2007:204–209.Google ScholarPubMed
Rezvani, K.PR1 vaccination in myeloid malignancies. Expert Rev Vaccines 2008;7:867–875.CrossRefGoogle ScholarPubMed
Stauss, HJ, Thomas, S, Cesco-Gaspere, M, et al. WT1-specific T cell receptor gene therapy: improving TCR function in transduced T cells. Blood Cells Mol Dis 2008;40:113–116.CrossRefGoogle ScholarPubMed
Shafer, JA, Cruz, CR, Leen, AM, et al. Antigen-specific cytotoxic T lymphocytes can target chemoresistant side-population tumor cells in Hodgkin lymphoma. Leuk Lymphoma 2010;51:870–880.CrossRefGoogle ScholarPubMed
Amrolia, PJ, Reid, SD, Gao, L, et al. Allorestricted cytotoxic T cells specific for human CD45 show potent antileukemic activity. Blood 2003;101:1007–1014.CrossRefGoogle ScholarPubMed
Till, BG, Jensen, MC, Wang, J, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008;112:2261–2271.CrossRefGoogle ScholarPubMed
Hambach, L, Goulmy, E.Immunotherapy of cancer through targeting of minor histocompatibility antigens. Curr Opin Immunol 2005;17:202–210.CrossRefGoogle ScholarPubMed
Oettel, KR, Wesly, OH, Albertini, MR, et al. Allogeneic T-cell clones able to selectively destroy Philadelphia chromosome-bearing (Ph1+) human leukemia lines can also recognize Ph1− cells from the same patient. Blood 1994;83:3390–3402.Google ScholarPubMed
Dermime, S, Bertazzoli, C, Marchesi, E, et al. Lack of T-cell mediated recognition of the fusion region of the pml/RAR: a hybrid protein by lymphocytes of acute promyelocytic leukemia patients. Clin Cancer Res 1996;2:593–600.Google ScholarPubMed
Molldrem, JJ, Lee, PP, Wang, C, et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000;6:1018–1023.CrossRefGoogle ScholarPubMed
Marijt, WA, Heemskerk, MH, Kloosterboer, FM, et al. Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci USA 2003;100:2742–2747.CrossRefGoogle ScholarPubMed
Alyea, EP, Soiffer, RJ, Canning, C, et al. Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998;91:3671–3680.Google ScholarPubMed
Giralt, S, Hester, J, Huh, Y, et al. CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood 1995;86:4337–4343.Google ScholarPubMed
Fowler, DH, Odom, J, Steinberg, SM, et al. Phase I clinical trial of costimulated, IL-4 polarized donor CD4+ T cells as augmentation of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006;12:1150–1160.CrossRefGoogle ScholarPubMed
Ciceri, F, Bonini, C, Stanghellini, MT, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I–II study. Lancet Oncol 2009;10:489–500.CrossRefGoogle ScholarPubMed
Laport, GG, Levine, BL, Stadtmauer, EA, et al. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin's lymphoma following CD34-selected hematopoietic cell transplantation. Blood 2003;102:2004–2013.CrossRefGoogle ScholarPubMed
Andre-Schmutz, I, Le Deist, F, Hacein-Bey-Abina, S, et al. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet 2002;360:130–137.CrossRefGoogle ScholarPubMed
Solomon, SR, Mielke, S, Savani, BN, et al. Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood 2005;106:1123–1129.CrossRefGoogle ScholarPubMed
Amrolia, PJ, Muccioli-Casadei, G, Huls, H, et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood 2006;108:1797–1808.CrossRefGoogle ScholarPubMed
Comoli, P, Labirio, M, Basso, S, et al. Infusion of autologous Epstein–Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 2002;99:2592–2598.CrossRefGoogle ScholarPubMed
Savoldo, B, Goss, JA, Hammer, MM, et al. Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). Blood 2006;108:2942–2949.CrossRefGoogle Scholar
Pulé, MA, Savoldo, B, Myers, GD, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 2008;14:1264–1270.CrossRefGoogle ScholarPubMed
Appelbaum, FR.Hematopoietic-cell transplantation at 50. N Engl J Med 2007;357:1472–1475.CrossRefGoogle ScholarPubMed
Papadopoulos, EB, Ladanyi, M, Emanuel, D, et al. Infusions of donor leukocytes to treat Epstein–Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N Engl J Med 1994;330:1185–1191.CrossRefGoogle ScholarPubMed
Heslop, HE, Brenner, MK, Rooney, CM. Donor T cells to treat EBV-associated lymphoma. N Engl J Med 1994;331:679–680.Google ScholarPubMed
Kolb, HJ, Mittermuller, J, Clemm, C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990;76:2462–2465.Google ScholarPubMed
Loren, AW, Porter, DL.Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation. Bone Marrow Transplant 2008;41:483–493.CrossRefGoogle ScholarPubMed
Schmid, C, Labopin, M, Nagler, A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 2007;25:4938–4945.CrossRefGoogle ScholarPubMed
Slavin, S, Naparstek, E, Nagler, A, et al. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood 1996;87:2195–2204.Google ScholarPubMed
Vago, L, Perna, SK, Zanussi, M, et al. Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med 2009;361:478–488.CrossRefGoogle ScholarPubMed
Leemhuis, T, Wells, S, Scheffold, C, Edinger, M, Negrin, RS.A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant 2005;11:181–187.CrossRefGoogle ScholarPubMed
Rapoport, AP, Stadtmauer, EA, Aqui, N, et al. Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of costimulated autologous T cells. Clin Cancer Res 2009;15:4499–4507.CrossRefGoogle ScholarPubMed
Mielke, S, Nunes, R, Rezvani, K, et al. A clinical scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique. Blood 2008;111:4392–4402.CrossRefGoogle Scholar
Tey, SK, Dotti, G, Rooney, CM, Heslop, HE, Brenner, MK.Inducible caspase 9 suicide gene to improve the safety of allodepleted T cells after haploidentical stem cell transplantation. Biol Blood Marrow Transplant 2007;13:913–924.CrossRefGoogle ScholarPubMed
Gottschalk, S, Ng, CYC, Smith, CA, et al. An Epstein–Barr virus deletion mutant that causes fatal lymphoproliferative disease unresponsive to virus-specific T cell therapy. Blood 2001;97:835–843.CrossRefGoogle Scholar
Khanna, R, Bell, S, Sherritt, M, Galbraith, A, et al. Activation and adoptive transfer of Epstein–Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proc Natl Acad Sci USA 1999;96:10391–10396.CrossRefGoogle ScholarPubMed
de Angelis, B, Dotti, G, Quintarelli, C, et al. Generation of Epstein–Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506). Blood 2009;114:4784–4791.CrossRefGoogle Scholar
Brewin, J, Mancao, C, Straathof, K, et al. Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease. Blood 2009;114:4792–4803.CrossRefGoogle ScholarPubMed
Haque, T, Wilkie, GM, Jones, MM, et al. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood 2007;110:1123–1131.CrossRefGoogle ScholarPubMed
Heslop, HE.How I treat EBV lymphoproliferation. Blood 2009;114:4002–4008.CrossRefGoogle Scholar
Bollard, CM, Aguilar, L, Straathof, KC, et al. Cytotoxic T lymphocyte therapy for Epstein–Barr virus+ Hodgkin's disease. J Exp Med 2004;200:1623–1633.CrossRefGoogle ScholarPubMed
Bollard, CM, Rossig, C, Calonge, MJ, et al. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood 2002;99:3179–3187.CrossRefGoogle ScholarPubMed
Mutis, T, Ghoreschi, K, Schrama, E, et al. Efficient induction of minor histocompatibility antigen HA-1-specific cytotoxic T-cells using dendritic cells retrovirally transduced with HA-1-coding cDNA. Biol Blood Marrow Transplant 2002;8:412–419.CrossRefGoogle ScholarPubMed
Montagna, D, Maccario, R, Locatelli, F, et al. Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy. Blood 2001;98:3359–3366.CrossRefGoogle ScholarPubMed
Falkenburg, JH, Wafelman, AR, Joosten, P, et al. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Blood 1999;94:1201–1208.Google ScholarPubMed
Duncan, C, Roddie, H.Dendritic cell vaccines in acute leukaemia. Best Pract Res Clin Haematol 2008;21:521–541.CrossRefGoogle ScholarPubMed
Banchereau, J, Palucka, AK.Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 2005;5:296–306.CrossRefGoogle ScholarPubMed
Timmerman, JM, Czerwinski, DK, Davis, TA, et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 2002;99:1517–1526.CrossRefGoogle ScholarPubMed
Hasan, AN, Kollen, WJ, Trivedi, D, et al. A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy. J Immunol 2009;183:2837–2850.CrossRefGoogle Scholar
Butler, MO, Lee, JS, Ansen, S, et al. Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell. Clin Cancer Res 2007;13:1857–1867.CrossRefGoogle ScholarPubMed
Berger, C, Jensen, MC, Lansdorp, PM, et al. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest 2008;118:294–305.CrossRefGoogle ScholarPubMed
Hinrichs, CS, Borman, ZA, Cassard, L, et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci USA 2009;106:17469–17474.CrossRefGoogle ScholarPubMed
Dotti, G, Savoldo, B, Brenner, M.Fifteen years of gene therapy based on chimeric antigen receptors: “are we nearly there yet?”. Hum Gene Ther 2009;20:1229–1239.CrossRefGoogle Scholar
Brenner, MK, Heslop, HE.Adoptive T cell therapy of cancer. Curr Opin Immunol 2010;22:251–257.CrossRefGoogle Scholar
Morgan, RA, Yang, JC, Kitano, M, et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizingErbB2. Mol Ther 2010;18:843–851.CrossRefGoogle ScholarPubMed
Traversari, C, Marktel, S, Magnani, Z, et al. The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies 4. Blood 2007;109:4708–4715.CrossRefGoogle ScholarPubMed
Hoyos, V, Savoldo, B, Quintarelli, C, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 2010;24: 1160–1170.CrossRefGoogle Scholar
Zou, W.Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 2005;5:263–274.CrossRefGoogle ScholarPubMed

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