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

  • CART and Immunotherapy (M Ruella, Section Editor)
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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.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. 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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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  Google Scholar 

  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  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Saar Gill.

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Saar Gill reports grants from Novartis Pharmaceuticals. In addition, Dr. Gill has a patent anti-CD19 CAR T cells in combination with small molecules pending to University of Pennsylvania.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Gill, S. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies. Curr Hematol Malig Rep 11, 318–325 (2016). https://doi.org/10.1007/s11899-016-0330-5

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