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01-08-2016 | CART and Immunotherapy (M Ruella, Section Editor)

Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies

Author: Saar Gill

Published in: Current Hematologic Malignancy Reports | Issue 4/2016

Abstract

Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

Smith CC, Wang Q, Chin C, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012;485(7397):260–3. doi:10.1038/nature11016.CrossRefPubMedPubMedCentral

Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293(5531):876–80. doi:10.1126/science.1062538.CrossRefPubMed

Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468:973–7. doi:10.1038/nature09626.CrossRefPubMedPubMedCentral

Cullen SP, Martin SJ. Mechanisms of granule-dependent killing. Cell Death Differ. 2007;15(2):251–62. doi:10.1038/sj.cdd.4402244.CrossRefPubMed

Barry M, Bleackley RC. Cytotoxic T lymphocytes: all roads lead to death. Nat Rev Immunol. 2002;2(6):401–9. doi:10.1038/nri819.PubMed

6.•

Sotillo E, Barrett DM, Black KL, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5(12):1282–95. doi:10.1158/2159-8290.CD-15-1020. This is the first description of the mechanism for loss of CD19 expression in patients treated with potent anti-CD19 directed immunotherapy.CrossRefPubMedPubMedCentral

Vago L, Perna SK, Zanussi M, et al. Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med. 2009;361(5):478–88. doi:10.1056/NEJMoa0811036.CrossRefPubMed

Schetelig J, van Biezen A, Brand R, et al. Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with p17 deletion: a retrospective European group for blood and marrow transplantation analysis. J Clin Oncol. 2008;26(31):5094–100. doi:10.1200/JCO.2008.16.2982.CrossRefPubMed

Osuji NC, Del Giudice I, Matutes E, Wotherspoon AC, Dearden C, Catovsky D. The efficacy of alemtuzumab for refractory chronic lymphocytic leukemia in relation to cytogenetic abnormalities of p53. Haematologica. 2005;90(10):1435–6.PubMed

10.

Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014;15(September):1090–9. doi:10.1016/S1470-2045(14)70335-3.CrossRefPubMedPubMedCentral

11.

Yoon KW, Byun S, Kwon E, et al. Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science. 2015;349(6247):1261669. doi:10.1126/science.1261669.CrossRefPubMed

12.•

Porter DL, Hwang W, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.CrossRefPubMed

13.•

Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(14):517–28. doi:10.1016/S0140-6736(14)61403-3.CrossRefPubMed

14.•

Kochenderfer JN, Dudley ME, Kassim SH, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540–9. doi:10.1200/JCO.2014.56.2025.CrossRefPubMed

15.•

Davila ML, Riviere I, Wang X, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6(224):224ra25. doi:10.1126/scitranslmed.3008226.CrossRefPubMedPubMedCentral

16.•

Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17. doi:10.1056/NEJMoa1407222. The above five references represent the current state-of-the-art descriptions of anti-CD19 CAR T cell therapy in a variety of settings.CrossRefPubMedPubMedCentral

17.

Huntington SF, Weiss BM, Vogl DT, et al. Financial toxicity in insured patients with multiple myeloma: a cross-sectional pilot study. Lancet Haematol. 2015;3026(15):1–9. doi:10.1016/S2352-3026(15)00151-9.

18.•

Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66. doi:10.1016/S1470-2045(14)71170-2. The largest study to date of patients with ALL receiving a bi-specific T cell engaging antibody, blinatumomab.CrossRefPubMed

19.

Goldman JM, Majhail NS, Klein JP, et al. Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase. J Clin Oncol. 2010;28(11):1888–95. doi:10.1200/JCO.2009.26.7757.CrossRefPubMedPubMedCentral

20.

Laport GG, Sheehan K, Baker J, et al. Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17(11):1679–87. doi:10.1016/j.bbmt.2011.05.012.CrossRefPubMedPubMedCentral

21.

Cichocki F, Cooley S, Davis Z, et al. CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT. Leukemia. 2015. doi:10.1038/leu.2015.260.PubMedPubMedCentral

22.

Bachanova V, Cooley S, Defor TE, et al. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014;123(25):3855–63. doi:10.1182/blood-2013-10-532531.CrossRefPubMedPubMedCentral

23.

Vallera DA, Felices M, McElmurry RT, et al. IL-15 trispecific killer engagers (TriKEs) make natural killer cells specific to CD33+ targets while also inducing in vivo expansion, and enhanced function. Clin Cancer Res. 2016. doi:10.1158/1078-0432.CCR-15-2710.PubMed

24.

Cichocki F, Verneris M, Cooley S, et al. The past, present and future of NK cells in hematopoietic cell transplantation and adoptive transfer. Curr Top Microbiol Immunol. 2016;395:225–43. doi:10.1007/82.PubMed

25.

Soiffer RJ, Lerademacher J, Ho V, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117(25):6963–70. doi:10.1182/blood-2011-01-332007.CrossRefPubMedPubMedCentral

26.

Venstrom JM, Pittari G, Gooley TA, et al. HLA-C–dependent prevention of leukemia relapse by donor activating KIR2DS1. N Engl J Med. 2012;367(9):805–16. doi:10.1056/NEJMoa1200503.CrossRefPubMedPubMedCentral

27.

Ruggeri L, Mancusi A, Capanni M, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110(1):433–40. doi:10.1182/blood-2006-07-038687.CrossRefPubMedPubMedCentral

28.

Griffioen M, van Bergen CAM, Falkenburg JHF. Autosomal minor histocompatibility antigens: how genetic variants create diversity in immune targets. Front Immunol. 2016;7:1–9. doi:10.3389/fimmu.2016.00100.CrossRef

29.

Van Bergen CAM, Rutten CE, Van Der Meijden ED, et al. High-throughput characterization of 10 new minor histocompatibility antigens by whole genome association scanning. Cancer Res. 2010;70(22):9073–83. doi:10.1158/0008-5472.CAN-10-1832.CrossRefPubMed

30.

Robinson TM, O’Donnell PV, Fuchs EJ, Luznik L. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol. 2016;53(2):90–7. doi:10.1053/j.seminhematol.2016.01.005.CrossRefPubMed

31.

Scott BL, Pasquini MC, Logan B et al. Results of a phase III randomized, multi-center study of allogeneic stem cell transplantation after high versus reduced intensity conditioning in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): blood and marrow transplant Cli. In: Presented at: 57th ASH Annual Meeting; December 4–7, 2015; Orlando, FL. Abstract LBA-8.

32.

Araki D, Wood BL, Othus M, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission? J Clin Oncol. 2016;34(4):329–36. doi:10.1200/JCO.2015.63.3826.CrossRefPubMed

33.

Rosenberg S, Lotze M, Muul L, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313(23):1485–92. doi:10.1056/NEJM198512053132327.CrossRefPubMed

34.

Shevach EM. Application of IL-2 therapy to target T regulatory cell function. Trends Immunol. 2012;33(12):626–32. doi:10.1016/j.it.2012.07.007.CrossRefPubMedPubMedCentral

35.

Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365:2055–66.CrossRefPubMedPubMedCentral

36.

Ma A, Koka R, Burkett P. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol. 2006;24:657–79. doi:10.1146/annurev.immunol.24.021605.090727.CrossRefPubMed

37.

Sportès C, Hakim FT, Memon SA, et al. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med. 2008;205(7):1701–14. doi:10.1084/jem.20071681.CrossRefPubMedPubMedCentral

38.

Sportès C, Babb RR, Krumlauf MC, et al. Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res. 2010;16(2):727–35. doi:10.1158/1078-0432.CCR-09-1303.CrossRefPubMedPubMedCentral

39.

Conlon KC, Lugli E, Welles HC, et al. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015;33(1):74–82. doi:10.1200/JCO.2014.57.3329.CrossRefPubMed

40.

Chester C, Fritsch K, Kohrt HE. Natural killer cell immunomodulation: targeting activating, inhibitory, and co-stimulatory receptor signaling for cancer immunotherapy. Front Immunol. 2015;6:601. doi:10.3389/fimmu.2015.00601.CrossRefPubMedPubMedCentral

41.

Benjamin JE, Gill S, Negrin RS. Biology and clinical effects of natural killer cells in allogeneic transplantation. Curr Opin Oncol. 2010;22(2):130–7. doi:10.1097/CCO.0b013e328335a559.CrossRefPubMedPubMedCentral

42.

Lundqvist A, Berg M, Smith A, Childs RW. Bortezomib treatment to potentiate the anti-tumor immunity of ex-vivo expanded adoptively infused autologous natural killer cells. J Cancer. 2011;2:383–5. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3133963&tool=pmcentrez&rendertype=abstract.CrossRefPubMedPubMedCentral

43.

Romee R, Maximillian R, Berrien-Elliott MM, et al. Human cytokine-induced memory-like NK cells exhibit in vivo anti-leukemia activity in xenografted NSG mice and in patients with acute myeloid leukemia (AML). Blood. 2015;126:101. Available at: http://www.bloodjournal.org/content/126/23/101.abstract.

44.

Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–4. doi:10.1126/science.1076514.CrossRefPubMedPubMedCentral

45.

Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346–57. doi:10.1200/JCO.2005.00.240.CrossRefPubMedPubMedCentral

46.

Dudley ME, Gross CA, Somerville RPT, et al. Randomized selection design trial evaluating CD8 + −enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol. 2013;31(17):2152–9. doi:10.1200/JCO.2012.46.6441.CrossRefPubMedPubMedCentral

47.

Noonan KA, Huff CA, Davis J, et al. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015;7(288):288ra78.CrossRefPubMedPubMedCentral

48.

Gros A, Parkhurst MR, Tran E, et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 2016. doi:10.1038/nm.4051.PubMed

49.•

Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641–5. doi:10.1126/science.1251102. Fascinating tour-de-force where next generation sequencing meets cellular immunotherapy.CrossRefPubMed

50.

Lesokhin AM, Callahan MK, Postow MA, Wolchok JD. STATE OF THE ART REVIEW on being less tolerant: enhanced cancer immuno surveillance enabled by targeting checkpoints and agonists of T cell activation. Sci Transl Med. 2015;7(280):1–12.CrossRef

51.

Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis. Cancer Treat Rev. 2016;45:30–7. doi:10.1016/j.ctrv.2016.02.006.CrossRefPubMed

52.

Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9. doi:10.1056/NEJMoa1411087.CrossRefPubMed

53.•

Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33. doi:10.1056/NEJMoa1302369. Clinical trial showing that response can be improved by combining two different checkpoint inhibitors.CrossRefPubMed

54.

Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014. doi:10.1056/NEJMoa1406498. 1–11.

55.

Kvistborg P, Philips D, Kelderman S, et al. Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. Sci Transl Med. 2014;6(254):254ra128–254ra128. doi:10.1126/scitranslmed.3008918.CrossRef

56.

Bollard CM, Gottschalk S, Torrano V, et al. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol. 2014;32(8):798–808. doi:10.1200/JCO.2013.51.5304.CrossRefPubMed

57.

Cruz CRY, Micklethwaite KP, Savoldo B, et al. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood. 2013;122(17):2965–73. doi:10.1182/blood-2013-06-506741.CrossRefPubMedPubMedCentral

58.

Ali SA, Shi V, Wang M, et al. Remissions of multiple myeloma during a first-in-humans clinical trial of T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor. In: Blood (ASH Annual Meeting Abstracts).Vol 126; 2015: LBA–1. Available at: http://www.bloodjournal.org/content/126/23/LBA-1.abstract.

59.

Fry TJ, Stetler-Stevenson M, Shah NN, et al. Clinical activity and persistence of anti-CD22 chimeric antigen receptor in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL) [Presented at ASH 2015]. In: Blood (ASH Annual Meeting Abstracts).Vol 126; 2015:1324. Available at: https://ash.confex.com/ash/2015/webprogram/Paper86307.html.

60.

Chapuis AG, Ragnarsson GB, Nguyen HN, et al. Transferred WT1-reactive CD8 + T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med. 2013;5(174):174ra27. doi:10.1126/scitranslmed.3004916.CrossRefPubMedPubMedCentral

61.

Aleksic M, Liddy N, Molloy PE, et al. Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies. Eur J Immunol. 2012;42(12):3174–9. doi:10.1002/eji.201242606.CrossRefPubMedPubMedCentral

62.

Nauerth M, Weißbrich B, Knall R, et al. TCR-ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer. Sci Transl Med. 2013;5(192):192ra87. doi:10.1126/scitranslmed.3005958.CrossRefPubMedPubMedCentral

63.

Kuball J, Dossett ML, Wolfl M, et al. Facilitating matched pairing and expression of TCR chains introduced into human T cells Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood. 2007;109:2331–8. doi:10.1182/blood-2006-05-023069.CrossRefPubMedPubMedCentral

64.

Kuball J, Hauptrock B, Malina V, et al. Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain. J Exp Med. 2009;206(2):463–75. doi:10.1084/jem.20082487.CrossRefPubMedPubMedCentral

65.

Li Y, Moysey R, Molloy PE, et al. Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nat Biotechnol. 2005;23(3):349–54. doi:10.1038/nbt1070.CrossRefPubMed

66.

Cameron BJ, Gerry AB, Dukes J, et al. Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med. 2013;5(197):197ra103. doi:10.1126/scitranslmed.3006034.CrossRefPubMed

67.

Linette GP, Stadtmauer EA, Maus MV, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013;122(6):863–71. doi:10.1182/blood-2013-03-490565.CrossRefPubMedPubMedCentral

68.

Bendle GM, Linnemann C, Hooijkaas AI, et al. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med. 2010;16(5):565–70. doi:10.1038/nm.2128.CrossRefPubMed

69.

Robbins PF, Morgan RA, Feldman SA, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011;29(7):917–24. doi:10.1200/JCO.2010.32.2537.CrossRefPubMedPubMedCentral

70.

Parkhurst MR, Yang JC, Langan RC, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther. 2011;19(3):620–6. doi:10.1038/mt.2010.272.CrossRefPubMed

71.

Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006;314(5796):126–9. doi:10.1126/science.1129003.CrossRefPubMedPubMedCentral

72.

Rapoport AP, Stadtmauer EA, Binder-Scholl GK, et al. NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):1–10. doi:10.1038/nm.3910.CrossRef

73.

Topp MS, Gökbuget N, Zugmaier G, et al. Study of blinatumomab in patients with MRD in B-lineage ALL brief report long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. 2013:5185–5187. doi:10.1182/blood-2012-07-441030.

74.•

Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520(7547):373–7. doi:10.1038/nature14292. Important paper describing the synergy from combining traditional with novel therapy for cancer.CrossRefPubMed

Title: Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies
Author: Saar Gill
Publication date: 01-08-2016
Publisher: Springer US
Published in: Current Hematologic Malignancy Reports / Issue 4/2016
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI: https://doi.org/10.1007/s11899-016-0330-5

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