Sharma P, Wagner K, Wolchok JD, Allison JP. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer. 2011;11:805–12.
Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015;14:561–84.
Topalian SL, Weiner GJ, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol. 2011;29:4828–36.
Sharma P, Allison JP. Immune checkpoint targeting in Cancer Therapy: toward combination strategies with curative potential. Cell. 2015;161:205–14.
Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480–9.
Yaddanapudi K, Mitchell RA, Eaton JW. Cancer vaccines. Oncoimmunology. 2013;2(3):e23403.
Pardoll DM, Topalian SL. The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol. 1998;10:588–94.
Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy. Moving beyond current vaccines. Nat Med. 2004;10:909–15.
Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity. 2013;39:38–48.
Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12:265–77.
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity Cycle. Immunity. 2013;39:1–10.
Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364:2119–27.
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.
Vansteenkiste J, Zilelinski M, Linder A, Dahabre J, Esteban E, Malinowski W, et al. Final results of a multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC). J Clin Oncol. 2007;25:abstract 7554.
Copier J, Dalgleish A. Whole-cell vaccines: A failure or a success waiting to happen? Curr Opin Mol Ther. 2010;12:14–20.
Schuler G. Dendritic cells in cancer immunotherapy. Eur J Immunol. 2010;40:2123–30.
Sabado RL, Bhardwaj N. Dendritic cell immunotherapy. Ann N Y Acad of Sci. 2013;1284:31–45.
Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115:3670–9.
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.
Fenoglio D, Traverso P, Parodi A, Kalli F, Zanetti M, Filaci G. Generation of more effective cancer vaccines. Hum Vaccin Immunother. 2013;9:2543–7.
Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens. A national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15:5323–37.
zur Hausen H. Papillomaviruses in the causation of human cancers: a brief historical account. Virology. 2009;384:260–5.
Greiner J, Bullinger L, Guinn BA, Dohner H, Schmitt M. Leukemia-associated antigens are critical for the proliferation of acute myeloid leukemia cells. Clin Cancer Res. 2008;14:7161–6.
Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen Y-C, Huang L-Q, et al. Mesothelin-specific CD8+ T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med. 2004;200:297–306.
Kasuga K. Comprehensive analysis of MHC ligands in clinical material by immunoaffinity-mass spectrometry. Methods Mol Biol. 2013;1023:203–18.
Rammensee H-G, Weinschenk T, Gouttefangeas C, Stevanovi Eq S. Towards patient-specific tumor antigen selection for vaccination. Immunol Rev. 2002;188:164–76.
Segal NH, Parsons DW, Peggs KS, Velculescu V, Kinzler KW, Vogelstein B, et al. Epitope landscape in breast and colorectal cancer. Cancer Res. 2008;68:889–92.
Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14:642–62.
Lichty BD, Breitbach CJ, Stojdl DF, Bell JC. Going viral with cancer immunotherapy. Nat Rev Cancer. 2014;14(8):559–67.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
Dharmadhikari N, Mehnert JM, Kaufman HL. Oncolytic virus immunotherapy for melanoma. Curr Treat Options Oncol. 2015;16:1–15.
DeWeese TL, van der Poel H, Li S, Mikhak B, Drew R, Goemann M, et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation Therapy. Cancer Res. 2001;61:7464–72.
Brown SM, MacLean AR, McKie EA, Harland J. The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34. J Virol. 1997;71:9442–9.
Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P, et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003;10:292–303.
Toda M, Martuza RL, Rabkin SD. Tumor growth inhibition by intratumoral inoculation of defective herpes simplex virus vectors expressing granulocyte-macrophage colony-stimulating factor. Mol Ther. 2000;2:324–29.
Hu JCC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ, et al. A phase I study of oncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 2006;12:6737–47.
Choi IK, Lee JS, Zhang SN, Park J, Lee KM, Sonn CH, et al. Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12R[beta]2 or IL-18R[alpha]. Gene Ther. 2011;18:898–909.
Lee Y-S, Kim J-H, Choi K-J, Choi I-K, Kim H, Cho S, et al. Enhanced antitumor effect of oncolytic adenovirus expressing interleukin-12 and B7-1 in an immunocompetent murine model. Clin Cancer Res. 2006;12:5859–68.
DeRubertis BG, Stiles BM, Bhargava A, Gusani NJ, Hezel M, D'Angelica M, et al. Cytokine-secreting herpes viral mutants effectively treat tumor in a murine metastatic colorectal liver model by oncolytic and T-cell-dependent mechanisms. Cancer Gene Ther. 2007;14:590–7.
Varghese S, Rabkin SD, Liu R, Nielsen PG, Ipe T, Martuza RL. Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers. Cancer Gene Ther. 2005;13:253–65.
Shin EJ, Wanna GB, Choi B, Aguila D, Ebert O, Genden EM, et al. Interleukin-12 expression enhances Vesicular stomatitis virus oncolytic therapy in murine squamous cell carcinoma. Laryngoscope. 2007;117:210–4.
Gaston DC, Odom CI, Li L, Markert JM, Roth JC, Cassady KA, et al. Production of bioactive soluble interleukin-15 in complex with interleukin-15 receptor alpha from a conditionally-replicating oncolytic HSV-1. PLoS One. 2013;8:e81768.
Stephenson KB, Barra NG, Davies E, Ashkar AA, Lichty BD. Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity. Cancer Gene Ther. 2012;19:238–46.
van Rikxoort M, Michaelis M, Wolschek M, Muster T, Egorov A, Seipelt J, et al. Oncolytic effects of a novel influenza A virus expressing interleukin-15 from the NS reading frame. PLoS One. 2012;7:e36506.
Fukuhara H, Ino Y, Kuroda T, Martuza RL, Todo T. Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome–mediated system. Cancer Res. 2005;65:10663–8.
Huang J-H, Zhang S-N, Choi K-J, Choi I-K, Kim J-H, Lee M, et al. Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL. Mol Ther. 2009;18:264–74.
Kim HS, Kim-Schulze S, Kim DW, Kaufman HL. Host lymphodepletion enhances the therapeutic activity of an oncolytic vaccinia virus expressing 4-1BB ligand. Cancer Res. 2009;69:8516–25.
Galivo F, Diaz RM, Diaz RM, Thanarajasingam U, Jevremovic D, Wongthida P, Thompson J, et al. Interference of CD40L-mediated tumor immunotherapy by oncolytic vesicular stomatitis virus. Human Gene Ther. 2010;21:439–50.
Tesfay MZ, Kirk AC, Hadac EM, Griesmann GE, Federspiel MJ, Barber GN, et al. PEGylation of vesicular stomatitis virus extends virus persistence in blood circulation of passively immunized mice. J Virol. 2013;87:3752–9.
Morrison J, Briggs SS, Green N, Fisher K, Subr V, Ulbrich K, et al. Virotherapy of ovarian cancer with polymer-cloaked adenovirus retargeted to the epidermal growth factor receptor. Mol Ther. 2007;16:244–51.
Berger C, Xuereb S, Johnson DC, Watanabe KS, Kiem H-P, Greenberg PD, et al. Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8+ cytotoxic T lymphocytes. J Virol. 2000;74:4465–73.
Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee SS, Yu J, et al. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci U S A. 2006;103:12873–8.
Chiocca EA, Rabkin SD. Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res. 2014;2:295–300.
Ledford H. Cancer-fighting viruses win approval. Nature. 2015;526:622–3.
Hersey P, Gallagher S. Intralesional immunotherapy for melanoma. J Surg Oncol. 2014;109:320–6.
Hercus TR, Thomas D, Guthridge MA, Ekert PG, King-Scott J, Parker MW, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood. 2009;11:1289–98.
Senzer NN, Kaufman HL, Amatruda T, Nemunaitis M, Reid T, Daniels G, et al. Phase II clinical trial of a ganulocyte-macrophage colony-stimulating factor–encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009;27:5763–71.
Kaufman HL, Kim DW, DeRaffele G, Mitcham J, Coffin RS, Kim-Schulze S. Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Ann Surg Oncol. 2009;17:718–30.
Kaufman HL, Bines SD. OPTIM trial: a phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. 2010;6:941–9.
Shi H, Qi X, Ma B, Cao Y, Wang L, Sun L, et al. The status, limitation and improvement of adoptive cellular immunotherapy in advanced urologic malignancies. Chin J Cancer Res. 2015;27:128–37.
Hinrichs CS, Rosenberg SA. Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol Rev. 2014;257:56–71.
Gilham DE, Anderson J, Bridgeman JS, Hawkins RE, Exley MA, Stauss H, et al. Adoptive T-cell therapy for cancer in the United Kingdom: a review of activity for the British Society of Gene and Cell Therapy annual meeting 2015. Hum Gene Ther. 2015;26:276–85.
Kazemi T, Younesi V, Jadidi-Niaragh F, Yousefi M. Immunotherapeutic approaches for cancer therapy: an updated review. Artif Cells Nanomed Biotechnol. 2015;24:1–11.
Yee C. Adoptive T-cell therapy for cancer: boutique therapy or treatment modality? Clin Cancer Res. 2013;19:4550–2.
Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298:850–4.
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.
Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005;202:907–12.
Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni L, Theoret MR, et al. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci U S A. 2004;101:1969–74.
Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17:4550–7.
Qian X, Wang X, Jin H. Cell transfer therapy for cancer: past, present, and future. J Immunol Res. 2014;2014:525913. doi:10.1155/2014/525913.
Morgan RA, Dudley ME, Rosenberg SA. Adoptive cell therapy: genetic modification to redirect effector cell specificity. Cancer J. 2010;16:336–41.
Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86:10024–8.
Drake CG, Jaffee E, Pardoll DM. Mechanisms of immune evasion by tumors. Adv Immunol. 2006;90:51–81.
Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–6.
Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991;74:561–9.
Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003;100:8372–7.
Ribas A. Releasing the brakes on cancer immunotherapy. N Engl J Med. 2015;373:1490–2.
Grosso JF, Jure-Kunkel MN, Jure-Kunkel MN. CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun. 2013;13:5.
Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain J-F, Testori A, Grob J-J, et al. Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. N Engl J Med. 2011;364(26):2517–26.
Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270(5238):985–8.
Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887–95.
Mary EK, Manish JB, Gordon JF, Arlene HS. PD-1 and Its Ligands in Tolerance and Immunity. Annu Rev Immunol. 2008;26(1):677–704.
Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14(12):1212–8.
Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–9.
Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2:261–8.
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020–30.
Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004;173:945–54.
Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25:9543–53.
Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian SL, 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.
Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, et al. LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med. 1990;171:1393–405.
Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207:2187–94.
Sierro S, Romero P, Speiser DE. The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin Ther Targets. 2011;15:91–101.
Brignone C, Escudier B, Grygar C, Marcu M, Triebel F. A phase I pharmacokinetic and biological correlative study of IMP321, a novel MHC class II agonist, in patients with advanced renal cell carcinoma. Clin Cancer Res. 2009;5:6225–31.
Brignone C, Gutierrez M, Mefti F, Brain E, Jarcau R, Cvitkovic F, et al. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity. J Transl Med. 2010;8:71. doi:10.1186/1479-5876-8-71.
Sanchez-Fueyo A, Tian J, Picarella D, Domenig C, Zheng XX, Sabatos CA, et al. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. 2003;4:1093–101.
Melero I, Berman DM, Aznar MA, Korman AJ, Gracia JLP, Haanen J. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer. 2015;15:457–72.
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.
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–33.
Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.
Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.
Melero I, Rouzaut A, Motz GT, Coukos G. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discovery. 2015;4:522–6.
Menard C, Martin F, Apetoh L, Bouyer F, Ghiringhelli F. Cancer chemotherapy: not only a direct cytotoxic effect, but also an adjuvant for antitumor immunity. Cancer Immunol Immunother. 2008;57:1579–87.
Moschella F, Proietti E, Capone I, Belardelli F. Combination strategies for enhancing the efficacy of immunotherapy in cancer patients. Ann NY Acad Sci. 2010;1194:169–78.
Le DT, Jaffee EM. Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: a current perspective. Cancer Res. 2012;72:3439–44.
Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T Cell-dependent antitumor immunity. Cancer Res. 2010;70(8):3052–61.
Sevko A, Michels T, Vrohlings M, Umansky L, Beckhove P, Kato M, et al. Antitumor effect of paclitaxel is mediated by inhibition of myeloid-derived suppressor cells and chronic inflammation in the spontaneous melanoma model. J Immunol. 2013;190:2464–71.
Alagkiozidis I, Facciabene A, Tsiatas M, Carpenito C, Benencia F, Adams S, et al. Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy. J Transl Med. 2011;9:77. doi:10.1186/1479-5876-9-77.
Machiels J-PH, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, et al. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized Mice. Cancer Res. 2001;61:3689–97.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.
Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J of Med. 2013;368:1365–6.
Ribas A BM, Butler M, Lutzky J, Lawrence DP, Robert C, Miller W, et al. Phase I study combining anti-PD-L1 (MEDI4736) with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma. J Clin Oncol. 2015;33 (Suppl; abstr 3003).
Minor DR, Puzanov I, Callahan MK, Hug BA, Hoos A. Severe gastrointestinal toxicity with administration of trametinib in combination with dabrafenib and ipilimumab. Pigment Cell Melanoma Res. 2015;28:611–2.
Comin-Anduix B, Chodon T, Sazegar H, Matsunaga D, Mock S, Jalil J, et al. The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability or function of human lymphocytes across a wide range of concentrations. Clin Cancer Res. 2010;16:6040–8.
Amin A, Plimack ER, Infante JR, Ernstoff MS, Rini BI, McDermott DF, et al. Nivolumab (anti-PD1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients 9pts0 with metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2014;32:5s. Suppl; abstr 5010.
Hodi FS, Lawrence D, Lezcano C, Wu X, Zhou J, Sasada T, et al. Bevacizumab plus ipilimumab in patients with metastatic melanoma. Cancer Immunol Res. 2014;2:632–42.
Chaudhary B, Khaled Y, Ammori B, Elkord E. Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother. 2014;63:81–99.
Papatriantafyllou M. T cells: neuropilin 1 distinguishing Treg cell subsets. Nat Rev Immunol. 2012;12:746–47.
Grandclement C, Borg C. Neuropilins: a new target for cancer therapy. Cancers (Basel). 2011;3:1899–928.
Weekes CD, Beeram M, Tolcher AW, Papadopoulos KP, Gore L, Hegde P, et al. A phase I study of the human monoclonal anti-NRP1 antibody MNRP1685A in patients with advanced solid tumors. Invest New Drugs. 2014;32:653–60.
Patnaik A, LoRusso P, Messersmith W, Papadopoulos K, Gore L, Beeram M, et al. A phase Ib study evaluating MNRP1685A, a fully human anti-NRP1 monoclonal antibody, in combination with bevacizumab and paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014;73:951–60.
Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, et al. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med. 1997;3:682–5.
Vinay DS, Kwon BS. Immunotherapy of cancer with 4-1BB. Mol Canc Ther. 2012;11:1062–70.
Ascierto PA, Simeone E, Sznol M, Fu Y-X, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol. 2010;37:508–16.
Kohrt HE, Colevas AD, Houot R, Weiskopf K, Goldstein MJ, Lund P, et al. Targeting CD137 enhances the efficacy of cetuximab. J Clin Invest. 2014;124:2668–82.
Takeda K, Kojima Y, Uno T, Hayakawa Y, Teng MWL, Yoshizawa H, et al. Combination therapy of established tumors by antibodies targeting immune activating and suppressing molecules. J Immunol. 2010;184:5493–501.
Curran MA, Kim M, Montalvo W, Al-Shamkhani A, Allison JP. Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PLoS One. 2011;6:e19499.
Youlin K, Li Z, Xiaodong W, Xiuheng L, Hengchen Z. Combination immunotherapy with 4-1BBL and CTLA-4 blockade for the treatment of prostate cancer. Clin Dev Immunol. 2012;2012:439235. doi:10.1155/439235.
Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, et al. Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res. 2012;72:3163–74.
Schaer DA, Hirschhorn-Cymerman D, Wolchok JD. Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy. J Immunother Cancer. 2014;2:7. doi:10.1186/2051-1426-2-7.
Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, et al. OX40 Is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013;73:7189–98.
Weinberg AD, Morris NP, Kovacsovics-Bankowski M, Urba WJ, Curti BD. Science gone translational: the OX40 agonist story. Immunol Rev. 2011;244:218–31.
Jensen SM, Maston LD, Gough MJ, Ruby CE, Redmond WL, Crittenden M, et al. Signaling through OX40 enhances antitumor immunity. Semin Oncol. 2010;37:524–32.
Bulliard Y, Jolicoeur R, Zhang J, Dranoff G, Wilson NS, Brogdon JL. OX40 engagement depletes intratumoral Tregs via activating Fc[gamma]Rs, leading to antitumor efficacy. Immunol Cell Biol. 2014;92:475–80.
Schaer DA, Murphy JT, Wolchok JD. Modulation of GITR for cancer immunotherapy. Curr Opin Immunol. 2012;24:217–24.
Cohen AD, Schaer DA, Liu C, Li Y, Hirschhorn-Cymmerman D, Kim SC, et al. Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS One. 2010;5:e10436.
Cai G, Freeman GJ. The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Immunol Rev. 2009;229:244–58.
Pasero C, Olive D. Interfering with coinhibitory molecules: BTLA/HVEM as new targets to enhance anti-tumor immunity. Immunol Letters. 2013;51:71–5.
Pasero C, Speiser DE, Derre L, Olive D. The HVEM network: new directions in targeting novel costimulatory/co-inhibitory molecules for cancer therapy. Curr Opin Pharmacol. 2012;12:478–85.
Derre L, Rivals JP, Jandus C, Pastor S, Rimoldi D, Romero P, et al. BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. J Clin Invest. 2010;120:157–67.
Fourcade J, Sun Z, Pagliano O, Guillaume P, Luescher IF, Sander C, et al. CD8+ T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res. 2012;72:887–96.
Melero I, Gaudernack G, Gerritsen W, Huber C, Parmiani G, Scholl S, et al. Therapeutic vaccines for cancer: an overview of clinical trials. Nat Rev Clin Oncol. 2014;11:509–24.
Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6:226ra32.
Puzanov I, Milhem MM, Andtbacka RHI, Minor DR, Hamid O, Li A, et al. Survival, safety, and response patterns in a phase 1b multicenter trial of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) in previously untreated, unresected stage IIIB-IV melanoma. J Clin Oncol. 2015;33(suppl; abstr 9063).
Johnson DB, Puzanov I, Kelley MC. Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. Immunotherapy. 2015;7:611–9.
Sznol M, Kluger HM, Callahan MK, Postow MA, Gordon RA, Segal NH, et al. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). J Clin Oncol. 2014;32:5s. suppl; abstr LBA9003^.
Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006–17.
Hodi F, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014;312(17):1744–53.
Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJM, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–12.
Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2014;30:2046–54.
Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013;24:75–83.
Cully M. Trial watch: combinations with checkpoint inhibitors at wavefront of cancer immunotherapy. Nat Rev Drug Discov. 2015;14:374–5.
Schumacher TN, Kesmir C, van Buuren MM. Biomarkers in cancer immunotherapy. Cancer Cell. 2015;27(1):12–4.
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8.
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SAJR, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–21.
Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350:207–11.
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015;5:43–51.
Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8. doi:10.1126/science.aaa1348.
Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, et al. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A. 2004;101:17174–9.
Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348:56–61.
Woo S-R, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012;72:917–27.