Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer

Journal for ImmunoTherapy of Cancer, Jun 2015

The pioneers of tumor immunology and cancer immunotherapy, including the late William B. Coley and Lloyd J. Old, have championed the potential for immunotherapy for over a century. Finally, advances in our understanding of the fundamentals of tumor immunology are translating into clinical success, with recent US Food and Drug Administration approval of several immunotherapies that improve clinical outcomes across prostate cancer, metastatic melanoma, non-small cell lung cancer and lymphocytic leukemia. In tandem with these clinical successes, new technologies such as high-throughput DNA/RNA sequencing, genetic engineering, and streamlined ex vivo cell culturing have paved the way for the next generation of immunotherapies and provided new tools for investigating potential biomarkers of response to existing therapies. During the November 2014 Annual Meeting of the Society of the Immunotherapy of Cancer, leaders in tumor immunology and cancer immunotherapy convened at the second annual SITC Primer to review both current knowledge and future directions in the field. Here, we will review the key discussions across a variety of topics, including innate immunity, adaptive immunity, dendritic cells, adoptive T cell therapy, anti-tumor antibodies, cancer vaccines, immune checkpoint blockade, challenges to immunotherapy, monitoring immune responses, and immunotherapy clinical trial design.

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Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer

Page et al. Journal for ImmunoTherapy of Cancer Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer David B. Page 0 Ariel Bulua Bourla 0 Anthony Daniyan 0 Jarushka Naidoo 0 Eric Smith 0 Melody Smith 0 Claire Friedman 0 Danny N. Khalil 0 Samuel Funt 0 Alexander N. Shoushtari 0 Willem W. Overwijk 1 Padmanee Sharma 1 Margaret K. Callahan 0 0 Memorial Sloan Kettering Cancer Center , 300 E 66th Street, BAIC 813, NY 10065 New York , USA 1 MD Anderson Cancer Center , Houston, TX , USA The pioneers of tumor immunology and cancer immunotherapy, including the late William B. Coley and Lloyd J. Old, have championed the potential for immunotherapy for over a century. Finally, advances in our understanding of the fundamentals of tumor immunology are translating into clinical success, with recent US Food and Drug Administration approval of several immunotherapies that improve clinical outcomes across prostate cancer, metastatic melanoma, non-small cell lung cancer and lymphocytic leukemia. In tandem with these clinical successes, new technologies such as high-throughput DNA/RNA sequencing, genetic engineering, and streamlined ex vivo cell culturing have paved the way for the next generation of immunotherapies and provided new tools for investigating potential biomarkers of response to existing therapies. During the November 2014 Annual Meeting of the Society of the Immunotherapy of Cancer, leaders in tumor immunology and cancer immunotherapy convened at the second annual SITC Primer to review both current knowledge and future directions in the field. Here, we will review the key discussions across a variety of topics, including innate immunity, adaptive immunity, dendritic cells, adoptive T cell therapy, anti-tumor antibodies, cancer vaccines, immune checkpoint blockade, challenges to immunotherapy, monitoring immune responses, and immunotherapy clinical trial design. CTLA4; PD-1; PD-L1; Melanoma; Prostate cancer; Kidney cancer; Bladder cancer; Lung cancer; Vaccine; Adoptive therapy; Nivolumab; Ipilimumab; Pembrolizumab; SITC; Primer - Introduction Clinical immunotherapy is undergoing a renaissance, with recent rapid-fire US Food and Drug Association (FDA) approval of numerous immunotherapies across several tumor types, including ipilimumab, pembrolizumab and nivolumab for metastatic melanoma, nivolumab for non-small cell squamous cell lung cancer, sipuleucel-T for prostate cancer, and blinatumomab for acute lymphocytic leukemia (ALL). In parallel, advances in research tools for basic and translational investigation have afforded an enhanced understanding of the fundamentals of tumor immunology, laying the foundation for subsequent development of the next generation of immunotherapeutic approaches. These approaches include therapeutic antibodies against novel targets, adoptive T-cell therapies, tumor vaccines, bispecific antibody constructs, and combination therapies. In November 2014, the Society for Immunotherapy of Cancer (SITC) held the second annual Primer on Tumor Immunology and Cancer Immunotherapy, organized by Drs. Willem W. Overwijk and Padmanee Sharma. In this review, we will summarize the key topics presented by the faculty, focusing upon recent advances in the field of immunotherapy. This year’s faculty included Dr. Vincenzo Bronte, MD (innate immunity), Dr. Lisa H. Butterfield, PhD (dendritic cells), Dr. Jonathan Powell, MD/PhD (adaptive immunity), Dr. Carl H. June, MD (adoptive T-cell therapy), Dr. Sattva S. Neelapu, MD (anti-tumor antibodies), Dr. Margaret K. Callahan, MD/PhD (obstacles to driving an immune response), Dr. Willem W. Overwijk, PhD (cancer vaccines), Dr. James P. Allison, PhD (targeting immune checkpoints in cancer therapy), Dr. Sasha Gnjatic, PhD (immune monitoring), and Dr. Padmanee Sharma, MD/PhD (pre-surgical clinical trial design). Innate immunity The innate immune system is evolutionarily conserved across both vertebrates and non-vertebrates, and provides a rapid, but non-specific, protective immune response to invading pathogens, The innate immune system responds within minutes and does not generate memory, but notably can stimulate and shape long-lasting antigen-specific immunity through a variety of mechanisms. Principal components of innate immunity include epithelial barriers (skin and mucosal membranes), pattern recognition receptors (PRRs), effector cells (monocytes/macrophages, natural killer (NK) cells, dendritic cells (DCs), mast cells, neutrophils, innate lymphoid cells, and eosinophils among others) and humoral components (complement proteins and collectins). The innate immune response can be initiated through activation of PRRs such as Toll-like receptors (TLR). These receptors can be extracellular, cytosolic, or endosomal. Pathogen associated molecular patterns (PAMP) are molecules shared by groups of pathogens (i.e. gram positive and gram negative bacteria), are not present in mammalian cells, and are capable of binding PRRs. These include b (...truncated)


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David Page, Ariel Bourla, Anthony Daniyan, Jarushka Naidoo, Eric Smith, Melody Smith, Claire Friedman, Danny Khalil, Samuel Funt, Alexander Shoushtari, Willem Overwijk, Padmanee Sharma, Margaret Callahan. Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer, Journal for ImmunoTherapy of Cancer, 2015, pp. 25, 3, DOI: 10.1186/s40425-015-0072-2