The expanding horizon of immunotherapy in the treatment of malignant disorders: Allogeneic hematopoietic stem cell transplantation and beyond

References

• Barnes DW, Corp MJ, Loutit JF, Neal FE. Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication. Br Med J. 1956;2:626–7.
   PubMed Web of Science ®Google Scholar
• Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–62.
   PubMed Web of Science ®Google Scholar
• Weisdorf D, Zhang M-J, Arora M, Horowitz M, Rizzo JD, Eapen M. Graft-versus-host disease induced graft-versus-leukemia effect: greater impact on relapse and disease-free survival after reduced intensity conditioning. Biol Blood Marrow Transplant. 2012;18:1727–33.
   PubMed Web of Science ®Google Scholar
• Nagler A, Labopin M, Shimoni A, Niederwieser D, Mufti GJ, Zander AR, et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012;18:1422–9.
   PubMedGoogle Scholar
• Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990; 76:2462–5.
   PubMed Web of Science ®Google Scholar
• Guglielmi C, Arcese W, Dazzi F, Brand R, Bunjes D, Verdonck LF, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood. 2002;100:397–405.
   PubMed Web of Science ®Google Scholar
• Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, et al. Graft-versus leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood. 1995;86:2041–50.
   PubMed Web of Science ®Google Scholar
• Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433–44.
   PubMed Web of Science ®Google Scholar
• Choi SJ, Lee JH, Kim S, Seol M, Lee YS, Lee JS, et al. Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullar relapse. Leukemia. 2004;18:1789–97.
   PubMed Web of Science ®Google Scholar
• Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas 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;25:4938–45.
   PubMed Web of Science ®Google Scholar
• Slavin S, Nagler A, Shapira MY, Aker M, Gabriel C, Or R. Treatment of leukemia by alloreactive lymphocytes and nonmyeloablative stem cell transplantation. J Clin Immunol. 2002;22:64–9.
   PubMed Web of Science ®Google Scholar
• Choi SJ, Lee JH, Kim S, Lee YS, Seol M, Ryu SG, et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant. 2005;36:163–9.
   PubMed Web of Science ®Google Scholar
• Collins RH Jr, Goldstein S, Giralt S, Levine J, Porter D, Drobyski W, et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 2000;26:511–16.
   PubMed Web of Science ®Google Scholar
• Bierman PJ, Sweetenham JW, Loberiza FR Jr, Taghipour G, Lazarus HM, Rizzo JD, et al. Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma: a comparison with allogeneic and autologous transplantation. J Clin Oncol. 2003;21:3744–53.
   PubMed Web of Science ®Google Scholar
• van de Donk NW, Kroger N, Hegenbart U, Corradini P, San Miguel JF, Goldschmidt H, et al. Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma. Bone Marrow Transplant. 2006;37:1135–41.
   PubMed Web of Science ®Google Scholar
• Shimoni A, Gajewski JA, Donato M, Martin T, O’Brien S, Talpaz M, et al. Long-term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant. 2001;7:568–75.
   PubMed Web of Science ®Google Scholar
• Soiffer R, Alyea E, Hochberg E, Wu C, Canning C, Parikh B, et al. Randomized trial of CD8 + T-cell depletion in the prevention of graft-versus-host disease associated with donor lymphocyte infusion. Biol Blood Marrow Transplant. 2002;8:625–32.
   PubMed Web of Science ®Google Scholar
• Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Zoumbos NC, et al. High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transplant. 2013;19:75–81.
   PubMed Web of Science ®Google Scholar
• Lutz C, Massenkeil G, Nagy M, Neuburger S, Tamm I, Rosen O, et al. A pilot study of prophylactic donor lymphocyte infusions to prevent relapse in adult acute lymphoblastic leukemias after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41:805–12.
   PubMed Web of Science ®Google Scholar
• Huang XJ, Wang Y, Liu DH, Xu LP, Chen H, Chen YH, et al. Modified donor lymphocyte infusion (DLI) for the prophylaxis of leukemia relapse after hematopoietic stem cell transplantation in patients with advanced leukemia—feasibility and safety study. J Clin Immunol. 2008;28:390–7.
   PubMed Web of Science ®Google Scholar
• Afzali B, Lechler RI, Hernandez-Fuentes MP. Allorecognition and the alloresponse: clinical implications. Tissue Antigens. 2007;69:545–6.
   PubMedGoogle Scholar
• Rezvani K, Barrett AJ. Characterizing and optimizing immune responses to leukaemia antigens after allogeneic stem cell transplantation. Best Pract Res Clin Haematol. 2008;21:437–53.
   PubMed Web of Science ®Google Scholar
• Falkenburg JH, Willemze R. Minor histocompatibility antigens as targets of cellular immunotherapy in leukaemia. Best Pract Res Clin Hematol. 2004;17:415–25.
   PubMed Web of Science ®Google Scholar
• Goulmy E, Schipper R, Pool J, Blokland E, Falkenburg JH, Vossen J, et al. Mismatches of minor histocompatibility antigens between HLA identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation. N Engl J Med. 1996; 334:281–5.
   PubMed Web of Science ®Google Scholar
• Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E. Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens. Blood. 1999;93:2336–41.
   PubMed Web of Science ®Google Scholar
• Bleakley M, Riddell SR. Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia. Immunol Cell Biol. 2011;89:396–407.
   PubMed Web of Science ®Google Scholar
• Fontaine P, Roy-Proulx G, Knafo L, Baron C, Roy DC, Perreault C. Adoptive transfer of T lymphocytes targeted to a single immunodominant minor histocompatibility antigen eradicates leukemia cells without causing graft-versus-host disease. Nat Med. 2001;7:789–94.
   PubMed Web of Science ®Google Scholar
• Blazar BR, Roopenian DC, Taylor PA, Christianson GJ, Panoskaltsis-Mortari A, Vallera DA. Lack of GVHD across classical, single minor histocompatibility (miH) locus barriers in mice. Transplantation. 1996; 61:619–24.
   Google Scholar
• Meunier M, Delisle J-S, Bergeron J, Rineau V, Baron C, Perreault C. T cells targeted against a single minor histocompatibility antigen can cure solid tumors. Nat Med. 2005;11:1222–9.
   PubMed Web of Science ®Google Scholar
• Jenkins MK, Chu HH, McLachlan JB, Moon JJ. On the composition of the preimmune repertoire of T cells specific for peptide-major histocompatibility complex ligands. Annu Rev Immunol. 2010;28: 275–94.
   PubMed Web of Science ®Google Scholar
• Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, et al. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplant with T cells specific for minor histocompatibility antigens. Blood. 2010;115:3869–78.
   PubMed Web of Science ®Google Scholar
• van Loenen M, de Boer R, Hagedoorn R, van Egmond E, Falkenburg F, Heemskerk M. Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies. Haematologica. 2011;96: 477–81.
   PubMed Web of Science ®Google Scholar
• Griffioen M, Honders W, van der Meijden E, van Luxemburg-Heijs S, Lurvink E, Kester M, et al. Identification of 4 novel HLA-B*40:01 restricted minor histocompatibility antigens and their potential as targets for graft-versus-leukemia reactivity. Haematologica. 2012;97:1196–204.
   Google Scholar
• Oostvogels R, Minnema MC, van Elk M, Spaapen RM, te Raa GT, Giovannone B, et al. Towards effective and safe immunotherapy after allogeneic stem cell transplantation: identification of hematopoietic-specific minor histocompatibility antigen UTA2-1. Leukemia. 2013; 27:642–9.
   PubMed Web of Science ®Google Scholar
• Sang M, Lian Y, Zhou X, Shan B. MAGE-A family: attractive targets for cancer immunotherapy. Vaccine. 2011;29:8496–500.
   PubMed Web of Science ®Google Scholar
• Williams RC Jr, Staud R, Malone CC, Payabyab J, Byres L, Underwood D. Epitopes on proteinase-3 recognized by antibodies from patients with Wegener's granulomatosis. J Immunol. 1994;152:4722–37.
   PubMed Web of Science ®Google Scholar
• Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE, et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med. 2000;6: 1018–23.
   PubMed Web of Science ®Google Scholar
• Qazilbash M, Wieder E, Thall P, Wang X, Rios R, Lu S, et al. PR1 peptide vaccine-induced immune response is associated with better event-free survival in patients with myeloid leukemia. Blood. 2007;110: Abstract 283.
   Google Scholar
• Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, et al. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood. 2009;113:6541–8.
   PubMed Web of Science ®Google Scholar
• Dao T, Yan S, Veomett N, Pankov D, Zhou L, Korontsvit T, et al. Targeting the Intracellular WT1 oncogene product with a therapeutic human antibody. Sci Transl Med. 2013;5:176ra33.
   Google Scholar
• Schmitt M, Schmitt A, Rojewski MT, Chen J, Giannopoulos K, Fei F, et al. RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood. 2008; 111:1357–65.
   PubMed Web of Science ®Google Scholar
• Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin Cancer Res. 2013;19: 4792–800.
   PubMed Web of Science ®Google Scholar
• Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Schallmach E, et al. Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother. 2009;32: 415–23.
   PubMed Web of Science ®Google Scholar
• Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006;314:126–9.
   PubMed Web of Science ®Google Scholar
• Robbins P, Morgan R, Feldman S, Yang J, Sherry R, Dudley M, 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;29:917–24.
   PubMed Web of Science ®Google Scholar
• Champlin R. T-cell depletion to prevent graft-versus-host disease after bone marrow transplantation. Hematol Oncol Clin N Am. 1990; 4:687–98.
   PubMed Web of Science ®Google Scholar
• Mielke S, Solomon SR, Barrett AJ. Selective depletion strategies in allogeneic stem cell transplantation. Cytotherapy. 2005;7:109–15.
   PubMed Web of Science ®Google Scholar
• Samarasinghe S, Mancao C, Pule M, Nawroly N, Karlsson H, Brewin J, et al. Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy. Blood. 2010;115:396–407.
   PubMed Web of Science ®Google Scholar
• Stuehler C, Mielke S, Chatterjee M, Duell J, Lurati S, Rueckert F, et al. Selective depletion of alloreactive T cells by targeted therapy of heat shock protein 90: a novel strategy for control of graft-versus-host disease. Blood. 2009;114:2829–36.
   PubMedGoogle Scholar
• Mielke S, Nunes R, Rezvani K, Fellowes VS, Venne A, Solomon SR, 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;111:4392–402.
   PubMed Web of Science ®Google Scholar
• Roy DC, Lachance S, Kiss T, Cohen S, Busque L, Fish D, et al. Haploidentical stem cell transplantation: high doses of alloreactive-T cell depleted donor lymphocytes administered post-transplant decrease infections and improve survival without causing severe GVHD. Blood. 2009;114: Abstract 512.
   Google Scholar
• Bonini C, Grez M, Traversari C, Ciceri F, Marktel S, Ferrari G, et al. Safety of retroviral gene marking with a truncated NGF receptor. Nat Med. 2003;9:367–9.
   PubMed Web of Science ®Google Scholar
• Ciceri F, Bonini C, Stanghellini M, Bondanza A, Traversari C, Salomoni M, 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.
   PubMed Web of Science ®Google Scholar
• Traversari C, Marktel S, Magnani Z, Mangia P, Russo V, Ciceri F, 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; 109:4708–15.
   PubMed Web of Science ®Google Scholar
• Ciceri F, Bonini C, Marktel S, Zappone E, Servida P, Bernardi M, et al. Antitumor effects of HSV-TK–engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood. 2007;109: 4698–707.
   PubMed Web of Science ®Google Scholar
• Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365:1673–83.
   PubMed Web of Science ®Google Scholar
• Tsirigotis P, Resnick IB, Shapira MY. The role of natural killer cells in hematopoietic stem cell transplantation. Ann Med. 2012;44: 130–45.
   PubMed Web of Science ®Google Scholar
• Nagler A, Greenberg PL, Lanier LL, Phillips JH. The effects of recombinant interleukin 2-activated natural killer cells on autologous peripheral blood hematopoietic progenitors. J Exp Med. 1988;168: 47–54.
   PubMed Web of Science ®Google Scholar
• Nagler A, Lanier LL, Phillips JH. Constitutive expression of high affinity interleukin 2 receptors on human CD16-natural killer cells in vivo. J Exp Med. 1990;171:1527–33.
   PubMed Web of Science ®Google Scholar
• Nagler A, Lanier LL, Cwirla S, Phillips JH. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989;143:3183–91.
   PubMed Web of Science ®Google Scholar
• Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, 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;313:1485–92.
   PubMed Web of Science ®Google Scholar
• Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, et al. Role of natural killer cell alloreactivity in HLA- mismatched hematopoietic stem cell transplantation. Blood. 1999;94: 333–9.
   PubMed Web of Science ®Google Scholar
• Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005; 105:3051–7.
   PubMed Web of Science ®Google Scholar
• Curti A, Ruggeri L, D’Addio A, Bontadini A, Dan E, Rosa M, et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood. 2011;118:3273–9.
   PubMed Web of Science ®Google Scholar
• Slavin S, Ackerstein A, Or R, Shapira MY, Gesundheit B, Askenasy N, et al. Immunotherapy in high-risk chemotherapy-resistant patients with metastatic solid tumors and hematological malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: a Phase 1 study. Cancer Immunol Immunother. 2010;59:1511–19.
   Google Scholar
• Slavin S, Or R, Aker M, Shapira MY, Resnick IB, Bitan M, et al. Treatment of resistant leukemia by rIL-2 activated NK cells in recipients of HLA matched and haploidentically mismatched stem cell allografts while avoiding GVHD. Blood. 2004;104: Abstract 5180.
   Google Scholar
• Koehl U, Sörensen J, Esser R, Zimmermann S, Grüttner HP, Tonn T, et al. IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation. Blood Cells Mol Dis. 2004; 33:261–6.
   PubMed Web of Science ®Google Scholar
• Passweg JR, Tichelli A, Meyer-Monard S, Heim D, Stern M, Kühne T, et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004;18:1835–38.
   PubMed Web of Science ®Google Scholar
• Stern M, Passweg JR, Meyer-Monard S, Esser R, Tonn T, Soerensen J, et al. Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers. Bone Marrow Transplantation. 2013;48:433–8.
   PubMed Web of Science ®Google Scholar
• Vey N, Bourhis J-H, Boissel N, Bordessoule D, Prebet T, Charbonnier A, et al. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission. Blood. 2012;120:4317–23.
   PubMed Web of Science ®Google Scholar
• Benson DM, Hofmeister CC, Padmanabhan S, Suvannasankha A, Jagannath S, Abonour R, et al. A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood. 2012;120:4324–33.
   PubMed Web of Science ®Google Scholar
• Baeuerle P, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009;69:4941–4.
   PubMed Web of Science ®Google Scholar
• Portell C, Wenzell C, Advani A. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clini Pharmacol. 2013;5(Suppl 1):5–11.
   Google Scholar
• Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321:974–7.
   PubMed Web of Science ®Google Scholar
• Topp MS, Gökbuget N, Zugmaier G, Degenhard E, Goebeler ME, Klinger M, et al. Long-term follow-up of hematologic relapse- free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120:5185–7.
   PubMed Web of Science ®Google Scholar
• Topp MS, Goekbuget N, Zugmaier G, Viardot A, Stelljes M, Neumann S, et al. Anti-CD19 BiTE blinatumomab induces high complete remission rate and prolongs overall survival in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). Blood. 2012;120: Abstract 670.
   Google Scholar
• Gleason M, Verneris M, Todhunter D, Zhang B, McCullar V, Zhou S, et al. Bispecific and trispecific killer cell engagers directly activate human NK cells through CD16 signaling and induce cytotoxicity and cytokine production. Mol Cancer Ther. 2012;11:2674–84.
   PubMed Web of Science ®Google Scholar
• Norde W, Hobo W, van der Voort R, Dolstra H. Coinhibitory molecules in hematologic malignancies: targets for therapeutic intervention. Blood. 2012;120:728–36.
   Google Scholar
• Piccirillo CA, Shevach EM. Cutting edge: control of CD8(+) T cell activation by CD4(+)CD25(+) immunoregulatory cells. J Immunol. 2001;167:1137–40.
   PubMed Web of Science ®Google Scholar
• Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell R, Zhou G, et al. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest. 2013;123:2447–63.
   PubMed Web of Science ®Google Scholar
• Lipson EJ, Drake CG. Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clin Cancer Res. 2011;17:6958–62.
   PubMed Web of Science ®Google Scholar
• Blazar BR, Taylor PA, Panoskaltsis-Mortari A, Sharpe AH, Vallera DA. Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells. J Immunol. 1999;162:6368–77.
   PubMed Web of Science ®Google Scholar
• Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Vrooman L, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009;113: 1581–8.
   PubMed Web of Science ®Google Scholar
• Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.
   PubMed Web of Science ®Google Scholar
• Topalian S, Hodi S, Brahmer J, Gettinger S, Smith D, McDermott D, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443–54.
   PubMed Web of Science ®Google Scholar
• Brahmer J, Tykodi S, Chow L, Hwu W-J, Topalian S, Hwu P, et al. Safety and activity of anti–PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455–65.
   PubMed Web of Science ®Google Scholar
• Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Chen YB, 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;31:4199–206.
   PubMed Web of Science ®Google Scholar
• Rozali E, Hato S, Robinson B, Lake R, Lesterhuis J. Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol. 2012;2012:656340.
   PubMedGoogle Scholar
• Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107:4275–80.
   PubMed Web of Science ®Google Scholar
• Chmielewski M, Hombach A, Abken H. Antigen-specificT-cell activation independently of the MHC: chimeric antigen receptor-redirected T cells. Front Immunol. 2013;4:371.
   PubMed Web of Science ®Google Scholar
• Davila M, Brentjens R, Wang X, Rivière I, Sadelain M. How do CARs work? Early insights from recent clinical studies targeting CD19. Oncoimmunology. 2012;1:1577–83.
   PubMed Web of Science ®Google Scholar
• Brentjens R. CARs and cancers: questions and answers. Blood, 2012 119:3872–3.
   Google Scholar
• Casucci M, di Robilant B, Falcone L, Camisa B, Norelli M, Genovese P, et al. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood. 2013;122: 3461–72.
   PubMed Web of Science ®Google Scholar
• Oberoi P, Wels W. Arming NK cells with enhanced antitumor activity CARs and beyond. Oncoimmunology. 2013;2:e25220.
   Google Scholar