Towards personalized, tumour-specific, therapeutic vaccines for cancer

Nature Reviews Immunology

Volumn 18, Issue 3, 2018, Pages 168-182

  Hu, Zhuting ^a   Ott, Patrick A ^a,b,c   Wu, Catherine J ^a,b,c,d  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATEZOLIZUMAB; CANCER TESTIS ANTIGEN; CANCER VACCINE; DENDRITIC CELL VACCINE; DNA VACCINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR VACCINE; IPILIMUMAB; MELANOMA ANTIGEN; NEOVAX; NIVOLUMAB; PEMBROLIZUMAB; PEPTIDE VACCINE; PROS VAC; PROSTATE SPECIFIC ANTIGEN; RACOTUMOMAB; RILIMOGENE GALVACIREPVEC; RNA VACCINE; TALIMOGENE LAHERPAREPVEC; TUMOR ANTIGEN; VIRUS ANTIGEN;

ADAPTIVE IMMUNITY; ADOPTIVE TRANSFER; ANTIGEN EXPRESSION; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; ANTINEOPLASTIC ACTIVITY; AUTOIMMUNITY; BRAIN CANCER; BREAST CANCER; CANCER IMMUNIZATION; CANCER STAGING; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CHRONIC LYMPHATIC LEUKEMIA; COLON CANCER; COLORECTAL CANCER; DRUG EFFICACY; DRUG RESPONSE; GLIOBLASTOMA; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; HUMORAL IMMUNITY; IMMUNE EVASION; IMMUNE RESPONSE; IMMUNITY; IMMUNOMODULATION; IMMUNOSTIMULATION; INNATE IMMUNITY; LIVER CELL CARCINOMA; LYMPHOCYTE SUBPOPULATION; MELANOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; OVERALL SURVIVAL; PANCREAS CANCER; PERSONALIZED MEDICINE; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; T LYMPHOCYTE; UTERINE CERVIX CANCER; VIRAL GENE DELIVERY SYSTEM; ADOPTIVE IMMUNOTHERAPY; IMMUNOLOGY; NEOPLASM; PROCEDURES; TRANSPLANTATION; VACCINATION;

CANCER VACCINES; HUMANS; IMMUNOTHERAPY, ADOPTIVE; NEOPLASMS; PRECISION MEDICINE; T-LYMPHOCYTES; VACCINATION;

EID: 85041594324     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri.2017.131     Document Type: Review

References (165)

1. Coulie, P. G., Van den Eynde, B. J., van der Bruggen, P. & Boon, T. Tumour antigens recognized by T lymphocytes: At the core of cancer immunotherapy. Nat. Rev. Cancer 14, 135-146 (2014).
2. Bachireddy, P., Burkhardt, U. E., Rajasagi, M. & Wu, C. J. Haematological malignancies: At the forefront of immunotherapeutic innovation. Nat. Rev. Cancer 15, 201-215 (2015).
3. Wong, K. K., Li, W. A., Mooney, D. J. & Dranoff, G. Advances in therapeutic cancer vaccines. Adv. Immunol. 130, 191-249 (2016).
4. Restifo, N. P., Dudley, M. E. & Rosenberg, S. A. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat. Rev. Immunol. 12, 269-281 (2012).
5. Rosenberg, S. A. & Restifo, N. P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348, 62-68 (2015).
6. Fesnak, A. D., June, C. H. & Levine, B. L. Engineered T cells: The promise and challenges of cancer immunotherapy. Nat. Rev. Cancer 16, 566-581 (2016).
7. Sharma, P. & Allison, J. P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell 161, 205-214 (2015).
8. Whiteside, T. L., Demaria, S., Rodriguez-Ruiz, M. E., Zarour, H. M. & Melero, I. Emerging opportunities and challenges in cancer immunotherapy. Clin. Cancer Res. 22, 1845-1855 (2016).
9. Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454 (2012).
10. Topalian, S. L. et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32, 1020-1030 (2014).
11. McDermott, D. F. et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J. Clin. Oncol. 33, 2013-2020 (2015).
12. Le, D. T. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409-413 (2017).
13. Nghiem, P. T. et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N. Engl. J. Med. 374, 2542-2552 (2016).
14. Ansell, S. M. et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 372, 311-319 (2015).
15. Le, D. T. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372, 2509-2520 (2015).
16. Brahmer, J. R. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455-2465 (2012).
17. Ott, P. A., Hodi, F. S., Kaufman, H. L., Wigginton, J. M. & Wolchok, J. D. Combination immunotherapy: A road map. J. Immunother. Cancer 5, 16 (2017).
18. Hegde, P. S., Karanikas, V. & Evers, S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin. Cancer Res. 22, 1865-1874 (2016).
19. Larkin, J. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23-34 (2015).
20. Postow, M. A. et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 372, 2006-2017 (2015).
21. Tran, E. et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344, 641-645 (2014).
22. Gubin, M. M. et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515, 577-581 (2014).
23. Kreiter, S. et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520, 692-696 (2015).
24. Rizvi, N. A. et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124-128 (2015).
25. Snyder, A. et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371, 2189-2199 (2014).
26. Schumacher, T. N. & Schreiber, R. D. Neoantigens in cancer immunotherapy. Science 348, 69-74 (2015).
27. Desrichard, A., Snyder, A. & Chan, T. A. Cancer neoantigens and applications for immunotherapy. Clin. Cancer Res. 22, 807-812 (2016).
28. Yadav, M. et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 515, 572-576 (2014).
29. Chen, D. S. & Mellman, I. Oncology meets immunology: The cancer-immunity cycle. Immunity 39, 1-10 (2013).
30. Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321-330 (2017).
31. Joffre, O. P., Segura, E., Savina, A. & Amigorena, S. Cross-presentation by dendritic cells. Nat. Rev. Immunol. 12, 557-569 (2012).
32. Zaretsky, J. M. et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375, 819-829 (2016).
33. Sharma, P., Hu-Lieskovan, S., Wargo, J. A. & Ribas, A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168, 707-723 (2017).
34. Meacham, C. E. & Morrison, S. J. Tumour heterogeneity and cancer cell plasticity. Nature 501, 328-337 (2013).
35. Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306-313 (2012).
36. Novellino, L., Castelli, C. & Parmiani, G. A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol. Immunother. 54, 187-207 (2005).
37. Buonaguro, L., Petrizzo, A., Tornesello, M. L. & Buonaguro, F. M. Translating tumor antigens into cancer vaccines. Clin. Vaccine Immunol. 18, 23-34 (2011).
38. Dudley, M. E. et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298, 850-854 (2002).
39. Theobald, M. et al. Tolerance to p53 by A2. 1-restricted cytotoxic T lymphocytes. J. Exp. Med. 185, 833-841 (1997).
40. Thaxton, J. E. & Li, Z. To affinity and beyond: harnessing the T cell receptor for cancer immunotherapy. Hum. Vaccin. Immunother. 10, 3313-3321 (2014).
41. Chen, Y. T. et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc. Natl Acad. Sci. USA 94, 1914-1918 (1997).
42. Stern, P. L. & Harrop, R. 5T4 oncofoetal antigen: An attractive target for immune intervention in cancer. Cancer Immunol. Immunother. 66, 415-426 (2017).
43. Melief, C. J., van Hall, T., Arens, R., Ossendorp, F. & van der Burg, S. H. Therapeutic cancer vaccines. J. Clin. Invest. 125, 3401-3412 (2015).
44. Kenter, G. G. et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N. Engl. J. Med. 361, 1838-1847 (2009).
45. Fritsch, E. F. et al. HLA-binding properties of tumor neoepitopes in humans. Cancer Immunol. Res. 2, 522-529 (2014).
46. Yarchoan, M., Johnson, B. A. 3rd, Lutz, E. R., Laheru, D. A. & Jaffee, E. M. Targeting neoantigens to augment antitumour immunity. Nat. Rev. Cancer 17, 209-222 (2017).
47. Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G. & Hacohen, N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160, 48-61 (2015).
48. Brown, S. D. et al. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res. 24, 743-750 (2014).
49. Giannakis, M. et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Res. 15, 857-865 (2016).
50. Howitt, B. E. et al. Association of polymerase e-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol. 1, 1319-1323 (2015).
51. Van Allen, E. M. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350, 207-211 (2015).
52. van Rooij, N. et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J. Clin. Oncol. 31, e439-e442 (2013).
53. Robbins, P. F. et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat. Med. 19, 747-752 (2013).
54. Tran, E. et al. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350, 1387-1390 (2015).
55. Linnemann, C. et al. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nat. Med. 21, 81-85 (2015).
56. Rajasagi, M. et al. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood 124, 453-462 (2014).
57. Matsushita, H. et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482, 400-404 (2012).
58. DuPage, M., Mazumdar, C., Schmidt, L. M., Cheung, A. F. & Jacks, T. Expression of tumour-specific antigens underlies cancer immunoediting. Nature 482, 405-409 (2012).
59. Castle, J. C. et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 72, 1081-1091 (2012).
60. Soiffer, R. et al. Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J. Clin. Oncol. 21, 3343-3350 (2003).
61. Vaishampayan, U., Abrams, J., Darrah, D., Jones, V. & Mitchell, M. S. Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon alpha. Clin. Cancer Res. 8, 3696-3701 (2002).
62. Dranoff, G. et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc. Natl Acad. Sci. USA 90, 3539-3543 (1993).
63. Jaffee, E. M. et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: A phase I trial of safety and immune activation. J. Clin. Oncol. 19, 145-156 (2001).
64. Le, D. T. et al. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J. Clin. Oncol. 33, 1325-1333 (2015).
65. Burkhardt, U. E. et al. Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells. J. Clin. Invest. 123, 3756-3765 (2013).
66. Ho, V. T. et al. Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation. Proc. Natl Acad. Sci. USA 106, 15825-15830 (2009).
67. Phan, V. et al. A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines. Nat. Med. 9, 1215-1219 (2003).
68. Rosenblatt, J. et al. Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions. Sci. Transl Med. 8, 368ra171 (2016).
69. Melero, I. et al. Therapeutic vaccines for cancer: An overview of clinical trials. Nat. Rev. Clin. Oncol. 11, 509-524 (2014).
70. Walter, S. et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat. Med. 18, 1254-1261 (2012).
71. Slingluff, C. L. Jr. et al. Immunologic and clinical outcomes of a randomized phase II trial of two multipeptide vaccines for melanoma in the adjuvant setting. Clin. Cancer Res. 13, 6386-6395 (2007).
72. Melief, C. J. & van der Burg, S. H. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat. Rev. Cancer 8, 351-360 (2008).
73. Ladjemi, M. Z. Anti-idiotypic antibodies as cancer vaccines: Achievements and future improvements. Front. Oncol. 2, 158 (2012).
74. Alfonso, S. et al. A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients. Clin. Cancer Res. 20, 3660-3671 (2014).
75. Srivastava, P. Roles of heat-shock proteins in innate and adaptive immunity. Nat. Rev. Immunol. 2, 185-194 (2002).
76. Ampie, L. et al. Heat shock protein vaccines against glioblastoma: from bench to bedside. J. Neuro. Oncol. 123, 441-448 (2015).
77. Hemmi, H. et al. A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745 (2000).
78. Yang, B., Jeang, J., Yang, A., Wu, T. C. & Hung, C. F. DNA vaccine for cancer immunotherapy. Hum. Vaccin. Immunother. 10, 3153-3164 (2014).
79. Zahm, C. D., Colluru, V. T. & McNeel, D. G. DNA vaccines for prostate cancer. Pharmacol. Ther. 174, 27-42 (2017).
80. Heil, F. et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526-1529 (2004).
81. Rittig, S. M. et al. Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients. Mol. Ther. 19, 990-999 (2011).
82. Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222-226 (2017).
83. Ott, P. A. & Hodi, F. S. Talimogene laherparepvec for the treatment of advanced melanoma. Clin. Cancer Res. 22, 3127-3131 (2016).
84. Kantoff, P. W. et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J. Clin. Oncol. 28, 1099-1105 (2010).
85. Pyzer, A. R., Avigan, D. E. & Rosenblatt, J. Clinical trials of dendritic cell-based cancer vaccines in hematologic malignancies. Hum. Vaccin. Immunother. 10, 3125-3131 (2014).
86. Palucka, K. & Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer 12, 265-277 (2012).
87. Mellman, I. & Steinman, R. M. Dendritic cells: specialized and regulated antigen processing machines. Cell 106, 255-258 (2001).
88. Maisonneuve, C., Bertholet, S., Philpott, J. & De Gregorio, E. Unleashing the potential of NOD-and Toll-like agonists as vaccine adjuvants. Proc. Natl Acad. Sci. USA 111, 12294-12299 (2014).
89. Dhodapkar, M. V. et al. Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci. Transl Med. 6, 232ra51 (2014).
90. Caskey, M. et al. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J. Exp. Med. 208, 2357-2366 (2011).
91. Sabbatini, P. et al. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin. Cancer Res. 18, 6497-6508 (2012).
92. Jiang, W. et al. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375, 151-155 (1995).
93. Bonifaz, L. C. et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 199, 815-824 (2004).
94. Cohn, L. et al. Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation. J. Exp. Med. 210, 1049-1063 (2013).
95. Vonderheide, R. H. & Glennie, M. J. Agonistic CD40 antibodies and cancer therapy. Clin. Cancer Res. 19, 1035-1043 (2013).
96. McWilliams, J. A., Sanchez, P. J., Haluszczak, C., Gapin, L. & Kedl, R. M. Multiple innate signaling pathways cooperate with CD40 to induce potent, CD70-dependent cellular immunity. Vaccine 28, 1468-1476 (2010).
97. Nimanong, S. et al. CD40 signaling drives potent cellular immune responses in heterologous cancer vaccinations. Cancer Res. 77, 1918-1926 (2017).
98. Schnurr, M. et al. ISCOMATRIX adjuvant induces efficient cross-presentation of tumor antigen by dendritic cells via rapid cytosolic antigen delivery and processing via tripeptidyl peptidase II. J. Immunol. 182, 1253-1259 (2009).
99. Wilson, N. S. et al. ISCOMATRIX vaccines mediate CD8+ T-cell cross-priming by a MyD88-dependent signaling pathway. Immunol. Cell Biol. 90, 540-552 (2012).
100. Davis, I. D. et al. Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans. Proc. Natl Acad. Sci. USA 101, 10697-10702 (2004).
101. Ragupathi, G., Gardner, J. R., Livingston, P. O. & Gin, D. Y. Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer. Expert Rev. Vaccines 10, 463-470 (2011).
102. Ishikawa, H. & Barber, G. N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455, 674-678 (2008).
103. Corrales, L. et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11, 1018-1030 (2015).
104. Chandra, D. et al. STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer. Cancer Immunol. Res. 2, 901-910 (2014).
105. Mitchell, D. A. et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature 519, 366-369 (2015).
106. Reed, S. G., Orr, M. T. & Fox, C. B. Key roles of adjuvants in modern vaccines. Nat. Med. 19, 1597-1608 (2013).
107. Hogenesch, H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front. Immunol. 3, 406 (2012).
108. Aucouturier, J., Dupuis, L., Deville, S., Ascarateil, S. & Ganne, V. Montanide ISA 720 and 51: A new generation of water in oil emulsions as adjuvants for human vaccines. Expert Rev. Vaccines 1, 111-118 (2002).
109. Fenstermaker, R. A. et al. Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. Cancer Immunol. Immunother. 65, 1339-1352 (2016).
110. Alving, C. R. Liposomes as carriers of antigens and adjuvants. J. Immunol. Methods 140, 1-13 (1991).
111. Neelapu, S. S. et al. Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen. Clin. Cancer Res. 10, 8309-8317 (2004).
112. Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489-496 (2017).
113. Moser, C., Muller, M., Kaeser, M. D., Weydemann, U. & Amacker, M. Influenza virosomes as vaccine adjuvant and carrier system. Expert Rev. Vaccines 12, 779-791 (2013).
114. Wiedermann, U. et al. A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: A phase I study. Breast Cancer Res. Treat. 119, 673-683 (2010).
115. Lynn, G. M. et al. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat. Biotechnol. 33, 1201-1210 (2015).
116. Gjerstorff, M. F., Andersen, M. H. & Ditzel, H. J. Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget 6, 15772-15787 (2015).
117. Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415-421 (2013).
118. Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546-1558 (2013).
119. Lawrence, M. S. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214-218 (2013).
120. Rosenberg, S. A., Yang, J. C. & Restifo, N. P. Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10, 909-915 (2004).
121. Nielsen, M. & Andreatta, M. NetMHCpan-3. 0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets. Genome Med. 8, 33 (2016).
122. Carreno, B. M. et al. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science 348, 803-808 (2015).
123. Ott, P. A. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217-221 (2017).
124. Fritsch, E. F., Hacohen, N. & Wu, C. J. Personal neoantigen cancer vaccines: The momentum builds. Oncoimmunology 3, e29311 (2014).
125. Stern, L. J. et al. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368, 215-221 (1994).
126. Rossjohn, J. et al. T cell antigen receptor recognition of antigen-presenting molecules. Annu. Rev. Immunol. 33, 169-200 (2015).
127. Mildner, A. & Jung, S. Development and function of dendritic cell subsets. Immunity 40, 642-656 (2014).
128. Gerner, M. Y., Casey, K. A., Kastenmuller, W. & Germain, R. N. Dendritic cell and antigen dispersal landscapes regulate T cell immunity. J. Exp. Med. 214, 3105-3122 (2017).
129. Robert, L. et al. CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Clin. Cancer Res. 20, 2424-2432 (2014).
130. Cha, E. et al. Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Sci. Transl Med. 6, 238ra70 (2014).
131. Tureci, O. et al. Targeting the heterogeneity of cancer with individualized neoepitope vaccines. Clin. Cancer Res. 22, 1885-1896 (2016).
132. Buonaguro, L. Developments in cancer vaccines for hepatocellular carcinoma. Cancer Immunol. Immunother. 65, 93-99 (2016).
133. Abelin, J. G. et al. Mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction. Immunity 46, 315-326 (2017).
134. Laidlaw, B. J., Craft, J. E. & Kaech, S. M. The multifaceted role of CD4+ T cells in CD8+ T cell memory. Nat. Rev. Immunol. 16, 102-111 (2016).
135. Nielsen, M., Lund, O., Buus, S. & Lundegaard, C. MHC class II epitope predictive algorithms. Immunology 130, 319-328 (2010).
136. Moynihan, K. D. et al. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat. Med. 22, 1402-1410 (2016).
137. van Elsas, A., Hurwitz, A. A. & Allison, J. P. 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 by autoimmune depigmentation. J. Exp. Med. 190, 355-366 (1999).
138. Duraiswamy, J., Kaluza, K. M., Freeman, G. J. & Coukos, G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 73, 3591-3603 (2013).
139. Ali, O. A., Lewin, S. A., Dranoff, G. & Mooney, D. J. Vaccines combined with immune checkpoint antibodies promote cytotoxic T-cell activity and tumor eradication. Cancer Immunol. Res. 4, 95-100 (2016).
140. Hodi, F. S. et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc. Natl Acad. Sci. USA 100, 4712-4717 (2003).
141. Soares, K. C. et al. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. J. Immunother. 38, 1-11 (2015).
142. Fu, J. et al. STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci. Transl Med. 7, 283ra52 (2015).
143. Melero, I. et al. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat. Rev. Cancer 15, 457-472 (2015).
144. Tzeng, A. et al. Temporally programmed CD8+ DC activation enhances combination cancer immunotherapy. Cell Rep. 17, 2503-2511 (2016).
145. Kim, J. et al. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 33, 64-72 (2015).
146. Ali, O. A. et al. Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants. Cancer Res. 74, 1670-1681 (2014).
147. Mijalis, A. J. et al. A fully automated flow-based approach for accelerated peptide synthesis. Nat. Chem. Biol. 13, 464-466 (2017).
148. Coley, W. B. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin. Orthop. Relat. Res. 262, 3-11 (1991).
149. Coley, W. B. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the Streptococcus erysipelas and the Bacillus prodigiosus). Proc. R. Soc. Med. 3, 1-48 (1910).
150. Hoover, H. C. et al. Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer. Cancer 55, 1236-1243 (1985).
151. van der Bruggen, P. et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254, 1643-1647 (1991).
152. Cox, A. L. et al. Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 264, 716-719 (1994).
153. Steinman, R. M. & Cohn, Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137, 1142-1162 (1973).
154. Hsu, F. J. et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat. Med. 2, 52-58 (1996).
155. Murphy, G., Tjoa, B., Ragde, H., Kenny, G. & Boynton, A. Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate 29, 371-380 (1996).
156. Nestle, F. O. et al. Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells. Nat. Med. 4, 328-332 (1998).
157. Kantoff, P. W. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411-422 (2010).
158. Cebon, J., Knights, A., Ebert, L., Jackson, H. & Chen, W. Evaluation of cellular immune responses in cancer vaccine recipients: lessons from NY-ESO-1. Expert Rev. Vaccines 9, 617-629 (2010).
159. Valmori, D. et al. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc. Natl Acad. Sci. USA 104, 8947-8952 (2007).
160. Landau, D. A. et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 152, 714-726 (2013).
161. Greenman, C. et al. Patterns of somatic mutation in human cancer genomes. Nature 446, 153-158 (2007).
162. Segal, N. H. et al. Epitope landscape in breast and colorectal cancer. Cancer Res. 68, 889-892 (2008).
163. George, S. et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity 46, 197-204 (2017).
164. Verdegaal, E. M. et al. Neoantigen landscape dynamics during human melanoma-T cell interactions. Nature 536, 91-95 (2016).
165. Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883-892 (2012).