The Human Vaccines Project: A roadmap for cancer vaccine development

A concerted international effort is necessary to achieve clinically effective cancer vaccines. Cancer vaccine development has been vigorously pursued for 40 years. Immunity to tumor antigens can be elicited by most vaccines tested, but their clinical efficacy remains modest. We argue that a concerted international effort is necessary to understand the human antitumor immune response and achieve clinically effective cancer vaccines.

[1]  David J Mooney,et al.  On-demand drug delivery from local depots. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Michael Dallas,et al.  Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial , 2015, The Lancet.

[3]  G. Giaccone,et al.  Why has active immunotherapy not worked in lung cancer? , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[4]  T. Gajewski.  The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment. , 2015, Seminars in oncology.

[5]  C. Slingluff,et al.  Vaccines, Adjuvants, and Dendritic Cell Activators--Current Status and Future Challenges. , 2015, Seminars in oncology.

[6]  K. Miller,et al.  Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study , 2015, Journal of Immunotherapy for Cancer.

[7]  J. Lunceford,et al.  Pembrolizumab for the treatment of non-small-cell lung cancer. , 2015, The New England journal of medicine.

[8]  E. Mardis,et al.  A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells , 2015, Science.

[9]  M. Kieny,et al.  Building the Human Vaccines Project: strategic management recommendations and summary report of the 15–16 July 2014 business workshop , 2015, Expert review of vaccines.

[10]  C. Drake,et al.  Immune checkpoint blockade: a common denominator approach to cancer therapy. , 2015, Cancer cell.

[11]  Martin L. Miller,et al.  Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer , 2015, Science.

[12]  T. Schumacher,et al.  Neoantigens in cancer immunotherapy , 2015, Science.

[13]  P. Knolle,et al.  Global transcriptional characterization of CD8+ T cell memory. , 2015, Seminars in immunology.

[14]  N. Hacohen,et al.  Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity , 2015, Cell.

[15]  Atul J. Butte,et al.  Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences , 2015, Cell.

[16]  L. Zitvogel,et al.  Trial Watch: Peptide-based anticancer vaccines , 2015, Oncoimmunology.

[17]  S. H. van der Burg,et al.  Vaccine-Induced Tumor Necrosis Factor–Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death , 2014, Clinical Cancer Research.

[18]  J. Wolchok,et al.  Genetic basis for clinical response to CTLA-4 blockade in melanoma. , 2014, The New England journal of medicine.

[19]  Z. Modrušan,et al.  Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing , 2014, Nature.

[20]  Maxim N. Artyomov,et al.  Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens , 2014, Nature.

[21]  D. Speiser,et al.  T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion? , 2014, Nature Reviews Immunology.

[22]  Özlem Türeci,et al.  mRNA-based therapeutics — developing a new class of drugs , 2014, Nature Reviews Drug Discovery.

[23]  B. Kyewski,et al.  Misinitiation of intrathymic MART‐1 transcription and biased TCR usage explain the high frequency of MART‐1‐specific T cells , 2014, European journal of immunology.

[24]  D. Speiser,et al.  Deciphering the unusual HLA‐A2/Melan‐A/MART‐1‐specific TCR repertoire in humans , 2014, European journal of immunology.

[25]  I. Melero,et al.  Therapeutic vaccines for cancer: an overview of clinical trials , 2014, Nature Reviews Clinical Oncology.

[26]  B. Pulendran.  Systems vaccinology: Probing humanity’s diverse immune systems with vaccines , 2014, Proceedings of the National Academy of Sciences.

[27]  W. Koff,et al.  Toward a Human Vaccines Project , 2014, Nature Immunology.

[28]  V. Bronte,et al.  Myeloid‐derived suppressor cell heterogeneity in human cancers , 2014, Annals of the New York Academy of Sciences.

[29]  James A. Williams.  Improving DNA vaccine performance through vector design. , 2014, Current gene therapy.

[30]  C. Slingluff,et al.  Current status of granulocyte–macrophage colony-stimulating factor in the immunotherapy of melanoma , 2014, Journal of Immunotherapy for Cancer.

[31]  G. Coukos,et al.  Tumor Endothelium FasL Establishes a Selective Immune Barrier Promoting Tolerance in Tumors , 2014, Nature Medicine.

[32]  Vincent Rouilly,et al.  Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli. , 2014, Immunity.

[33]  P. Coulie,et al.  Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy , 2014, Nature Reviews Cancer.

[34]  E. Gilboa,et al.  Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity. , 2014, The Journal of clinical investigation.

[35]  P. Romero,et al.  Adjuvants that improve the ratio of antigen-specific effector to regulatory T cells enhance tumor immunity. , 2013, Cancer research.

[36]  S. H. van der Burg,et al.  Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T‐cell activation , 2013, European journal of immunology.

[37]  G. Coukos,et al.  Deciphering and reversing tumor immune suppression. , 2013, Immunity.

[38]  A. Legat,et al.  T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion , 2013, Nature Immunology.

[39]  Philip R. Johnson,et al.  Accelerating Next-Generation Vaccine Development for Global Disease Prevention , 2013, Science.

[40]  J. Rothman,et al.  Live-attenuated Listeria-based immunotherapy , 2013, Expert review of vaccines.

[41]  Susan M. Kaech,et al.  Transcriptional control of effector and memory CD8+ T cell differentiation , 2012, Nature Reviews Immunology.

[42]  D. Lowy,et al.  Understanding and learning from the success of prophylactic human papillomavirus vaccines , 2012, Nature Reviews Microbiology.

[43]  E. Jaffee,et al.  Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: a current perspective. , 2012, Cancer research.

[44]  Karolina Palucka,et al.  Cancer immunotherapy via dendritic cells , 2012, Nature Reviews Cancer.

[45]  Qingsheng Li,et al.  Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation. , 2012, Immunity.

[46]  C. Ottensmeier,et al.  DNA fusion vaccines enter the clinic , 2011, Cancer Immunology, Immunotherapy.

[47]  R. Steinman,et al.  Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A , 2011, Proceedings of the National Academy of Sciences.

[48]  E. Klechevsky,et al.  Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR. , 2010, Blood.

[49]  J. Yewdell.  Designing CD8+ T cell vaccines: it's not rocket science (yet). , 2010, Current opinion in immunology.

[50]  D. Speiser,et al.  Molecularly defined vaccines for cancer immunotherapy, and protective T cell immunity. , 2010, Seminars in immunology.

[51]  P. Kantoff,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. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  S. H. van der Burg,et al.  Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. , 2009, The New England journal of medicine.

[53]  Martin A. Cheever,et al.  The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research , 2009, Clinical Cancer Research.

[54]  A. Eggermont.  Therapeutic vaccines in solid tumours: can they be harmful? , 2009, European journal of cancer.

[55]  Russell G. Jones,et al.  Enhancing CD8 T-cell memory by modulating fatty acid metabolism , 2009, Nature.

[56]  R. Ahmed,et al.  mTOR regulates memory CD8 T cell differentiation , 2009, Nature.

[57]  M. Neller,et al.  Antigens for cancer immunotherapy. , 2008, Seminars in immunology.

[58]  B. Kyewski,et al.  Promiscuous gene expression patterns in single medullary thymic epithelial cells argue for a stochastic mechanism , 2008, Proceedings of the National Academy of Sciences.

[59]  R. Elashoff,et al.  An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites , 2007 .

[60]  D. Tough,et al.  Preferential Induction of CD4+ T Cell Responses through In Vivo Targeting of Antigen to Dendritic Cell-Associated C-Type Lectin-1 , 2006, The Journal of Immunology.

[61]  J. Berzofsky,et al.  Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[62]  F. Pijpers,et al.  Therapeutic cancer vaccines , 2005, Nature Reviews Drug Discovery.

[63]  D. Speiser,et al.  Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. , 2005, The Journal of clinical investigation.

[64]  S. Rosenberg,et al.  Cancer immunotherapy: moving beyond current vaccines , 2004, Nature Medicine.

[65]  H. von Boehmer,et al.  In Vivo Instruction of Suppressor Commitment in Naive T Cells , 2004, The Journal of experimental medicine.

[66]  W. Lehmacher,et al.  Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial , 2004, The Lancet.

[67]  M. Pfreundschuh,et al.  Human neoplasms elicit multiple specific immune responses in the autologous host. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[68]  P. Chomez,et al.  A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. , 1991, Science.