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Expert Review of Hematology Volume 9, 2016 - Issue 2
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Review

Beginning of a novel frontier: T-cell-directed immune manipulation in lymphomas

Benjamin KasendaDepartment of Medicine, Royal Marsden Hospital, Sutton, UK
,
Andrea KühnlDepartment of Medicine, Royal Marsden Hospital, Sutton, UK
&
Ian ChauDepartment of Medicine, Royal Marsden Hospital, Sutton, UKCorrespondence[email protected]
Pages 123-135 | Received 27 Jul 2015, Accepted 17 Nov 2015, Published online: 06 Jan 2016

References

• First randomized trial showing significant activity of ipilimumab.

  • Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526.
  • Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–330.

• Randomized phase III trial proving superiority of Nivolumab versus Dacarbazine in newly diagnosed advanced melanoma.

  • Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;2045:1–10.
  • Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–2532.
  • Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hemat Am Soc Hematol Educ Prog. 2011;2011:498–505.
  • Casulo C, Burack WR, Friedberg JW. Transformed follicular non-Hodgkin lymphoma. Blood. 2015;125(1):40–48.
  • Fisher RI, Khan N. Is observation dead in follicular lymphoma ? No, but the apoptosis pathway has been activated. J Natl Compr Canc Netw. 2015;13(3):363–366.
  • Dreyling M, Ghielmini M, Marcus R, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii76–82.
  • Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.
  • Bour-Jordan H, Esensten JH, Martinez-Llordella M, et al. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 family. Immunol Rev. 2011;241(1):180–205.
  • Schneider H, Downey J, Smith A, et al. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313(5795):1972–1975.
  • Riley JL, Mao M, Kobayashi S, et al. Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc Natl Acad Sci U S A. 2002;99(18):11790–11795.
  • Qureshi OS, Zheng Y, Nakamura K, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332(6029):600–603.
  • Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270(5238):985–988.
  • Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3(5):541–547.
  • Van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied. J Exp Med. 1999;190(3):355–366.
  • Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734–1736.
  • Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.
  • Hardy B, Niv Y, Fadaeev L, et al. BAT mAb induces lymphopoiesis in nude mice. Int Immunol. 2005;17(5):615–619.
  • Hardy B, Indjiia L, Rodionov G, et al. Treatment with BAT monoclonal antibody decreases tumor burden in a murine model of leukemia/lymphoma. Int J Oncol. 2001;19(5):897–902.
  • Curiel TJ, Wei S, Dong H, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med. 2003;9(5):562–567.
  • Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol. 2005;17(2):133–144.
  • Hardy B, Yampolski I, Kovjazin R, et al. A monoclonal antibody against a human B lymphoblastoid cell line induces tumor regression in mice. Cancer Res. 1994;54(22):5793–5796.
  • Hirano F, Kaneko K, Tamura H, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 2005;65(3):1089–1096.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.

• Randomized phase III trial showing that combination of Nivolumab and Ipilimumab is superior to each single agent.

  • Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med. 2015;373(2):123–135.
  • Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116(17):3268–3277.
  • Juszczynski P, Ouyang J, Monti S, et al. The AP1-dependent secretion of galectin-1 by reed sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci USA. 2007;104(32):13134–13139.
  • Steidl C, Shah SP, Woolcock BW, et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature. 2011;471(7338):377–381.
  • 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):311–319.

•• First non-randomized trial showing high activity of single agent Nivolumab in heavily pre-treated Hodgkin lymphoma patients.

  • Dave SS, Wright G, Tan B, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351(21):2159–2169.
  • Wahlin BE, Sander B, Christensson B, et al. CD8+ T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma. Clin Cancer Res. 2007;13(2 I):388–397.
  • Álvaro-Naranjo T, Lejeune M, Salvadó MT, et al. Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients. J Clin Oncol. 2006;24(34):5350–5357.
  • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
  • Myklebust JH, Irish JM, Brody J, et al. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood. 2013;121(8):1367–1376.
  • Keam B, Ha H, Kim TM, et al. Neutrophil to lymphocyte ratio improves prognostic prediction of international prognostic index for patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma. 2015;August 2014:1–7.
  • Koh YW, Kang HJ, Park C, et al. Prognostic significance of the ratio of absolute neutrophil count to absolute lymphocyte count in classic Hodgkin lymphoma. Am J Clin Pathol. 2012;138:846–854.
  • Porrata LF, Ristow K, Habermann T, et al. Predicting survival for diffuse large B-cell lymphoma patients using baseline neutrophil/lymphocyte ratio. Am J Hematol. 2010;85(11):896–899.
  • Troppan K, Deutsch A, Gerger A, et al. The derived neutrophil to lymphocyte ratio is an independent prognostic factor in patients with diffuse large B-cell lymphoma. Br J Cancer Nat Pub Group. 2014;110(2):369–374.
  • Watanabe R, Tomita N, Itabashi M, et al. Peripheral blood absolute lymphocyte/monocyte ratio as a useful prognostic factor in diffuse large B-cell lymphoma in the rituximab era. Eur J Haematol. 2014;92:204–210.
  • Bashey A, Medina B, Corringham S, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009;113(7):1581–1588.
  • Ansell SM, Hurvitz SA, Koenig PA, et al. Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2009;1515(20):6446–6453.
  • Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14(10):3044–3051.
  • Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large b-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31(33):4199–4206.
  • Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012/10/24 ed.; 2012;30(36):4462–4469.
  • Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol. Elsevier Ltd; 2014;15(1):69–77.

•• First non-randomized trial showing activity of Pidilizumab in combination with Rituximab in follicular lymphoma.

  • Lesokhin AM, Ansell SM, Armand P, et al. Preliminary results of a phase i study of nivolumab (BMS‐936558) in patients with relapsed or refractory lymphoid malignancies. Blood. 2014;124:abstract 291.
  • Moskowitz CH, Ribrag V, Michot J-M, et al. PD‐1 blockade with the monoclonal antibody pembrolizumab (MK‐3475) in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE‐013). Blood. 2014;124:abstract 290.
  • Ribas A, Robert C, Hodi FS, et al. Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature. J Clin Oncol. 2015;33:abstract 3001.
  • Hawkes EA, Grigg A, Chong G. Programmed cell death-1 inhibition in lymphoma. Lancet Oncol Elsevier Ltd. 2015;16(5):e234–45.
  • Xerri L, Chetaille B, Seriari N, et al., Programmed death 1 is a marker of angioimmunoblastic T-cell lymphoma and B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. Hum Pathol. 2008;39(7):1050–1058.
  • Dorfman DM, Brown JA, Shahsafaei A, et al. Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma. Am J Surg Pathol. 2006;30(7):802–810.
  • Han L, Liu F, Li R, et al. Role of programmed death ligands in effective T-cell interactions in extranodal natural killer/T-cell lymphoma. Oncol Lett. 2014;8(4):1461–1469.
  • Andorsky DJ, Yamada RE, Said J, et al. Programmed death ligand 1 is expressed by non-Hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011;17(13):4232–4244.
  • Yamamoto R, Nishikori M, Kitawaki T, et al., PD-1 PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood. 2008;111(6):3220–3224.
  • Rossille D, Gressier M, Damotte D, et al., High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-cell lymphoma: results from a French multicenter clinical trial. Leukemia. 2014;28(12):2367–2375.
  • Chen BJ, Chapuy B, Ouyang J, et al., PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19(13):3462–3473.
  • Rosenberg SA, Yang JC, Sherry RM, et al., Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–4557.
  • Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269–281.
  • Eshhar Z, Waks T, Gross G, et al. 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. Proc Natl Acad Sci USA. 1993;90(2):720–724.
  • Curran KJ, Brentjens RJ. Chimeric antigen receptor T cells for cancer immunotherapy. J Clin Oncol. 2015;33(15):1703–1706.
  • Hombach A, Sent D, Schneider C, et al., T-cell activation by recombinant receptors: CD28 costimulation is required for interleukin 2 secretion and receptor-mediated T-cell proliferation but does not affect receptor-mediated target cell lysis. Cancer Res. 2001;61(5):1976–1982.
  • Hombach A, Wieczarkowiecz A, Marquardt T, et al., Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol. 2001;167(11):6123–6131.
  • Finney HM, Lawson AD, Bebbington CR, et al. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol. 1998;161(6):2791–2797.
  • Finney HM, Akbar AN, Lawson ADG. 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. J Immunol. 2004;172(1):104–113.
  • Maher J, Brentjens RJ, Gunset G, et al. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol. 2002;20(1):70–75.
  • Imai C, Mihara K, Andreansky M, et al., Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leuk Off J Leuk Soc Am Leuk Res Fund, UK. 2004;18(4):676–684.
  • Haynes NM, Trapani JA, Teng MWL, et al., Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors. Blood. 2002;100(9):3155–3163.
  • Carpenito C, Milone MC, Hassan R, et al., Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci USA. 2009;106(9):3360–3365.
  • Brentjens RJ, Santos E, Nikhamin Y, et al., Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2007;13(18):5426–5435.
  • Savoldo B, Ramos CA, Liu E, et al., CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011;121(5):1822–1826.
  • 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.
  • 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):1507–1517.

•• Relatively large study on CTL019 in relapsed acute lymphoblastic leukemia in children.

  • Rambaldi A, Biagi E, Bonini C, et al. Cell-based strategies to manage leukemia relapse: efficacy and feasibility of immunotherapy approaches. Leukemia. 2015;29(1):1–10.
  • Emole JN, Locke FL, Pinilla-Ibarz J. An update on current and prospective immunotherapies for chronic lymphocytic leukemia. Immunotherapy. 2015;7(4):455–466.
  • 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):540–549.

•• Relatively large study on CAR-T cell treatment in relapsed/refractory B-cell lymphomas.

  • Brentjens RJ, Rivière I, Park JH, et al., Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011;118(18):4817–4828.
  • Schuster SJ, Svoboda J, Nasta S, et al., Phase IIa trial of chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas. J Clin Oncol. 2015;33:abstract 8.
  • Davila ML, Kloss CC, Gunset G, et al. CD19 CAR-targeted T cells induce long-term remission and B cell aplasia in an immunocompetent mouse model of b cell acute lymphoblastic leukemia. PLoS One. 2013;8(4):e61338.
  • Brentjens RJ, Davila ML, Riviere I, et al., CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra38.
  • Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–1518.

•• First case reports on the use of CTL09 in paediatric patients with relapsed acute lymphoblastic leukemia.

  • Bonini C. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science (80-). 1997;276(5319):1719–1724.
  • 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. Blood. 2007;109(11):4708–4715.
  • Philip B, Kokalaki E, Mekkaoui L, et al., A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124(8):1277–1287.
  • Wang X, Chang WC, Wong CW, et al. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood. 2011;118(5):1255–1263.
  • Moroz MA, Zhang H, Lee J, et al. Comparative analysis of T cell imaging with human nuclear reporter genes. J Nucl Med. 2015;56(7):1055–1060.
  • Vesely MD, Kershaw MH, Schreiber RD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–271.
  • Pegram HJ, Lee JC, Hayman EG, et al., Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood. 2012;119(18):4133–4141.
  • Jensen MC, Popplewell L, Cooper LJ, et al. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transplant. 2010;16(9):1245–1256.
  • Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725–733.
  • Kochenderfer JN, Dudley ME, Carpenter RO, et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood. 2013;122(25):4129–4139.

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