Getting to know I-O

   Why the excitement?

Madan RA, Gulley JL. (R)Evolutionary Therapy: The Potential of Immunotherapy to Fulfill the Promise of Personalized Cancer Treatment. J Nat Cancer Inst. 2015;107(1):1-4.

A provocative, well written commentary exploring the authors' expectation for immunotherapy to transform the treatment of cancer. A must read. 

   The Beginnings

Hall, SS. A Commotion in the Blood: Life, Death, and the Immune System. Henry Holt & Co, 1997.

A well researched and written book detailing the history of immunological approaches to cancer therapy, beginning with Coley's toxins more than a century ago and continuing through the early 1990s.

Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991-8. [article for purchase]

Dunn GP, Old LJ, Schreiber RD. The Immunobiology of Cancer Immunosurveillance and Immunoediting. Immunity. 2004;21(2):137-48.

These reviews provide the theoretical basis for understanding the important - and previously largely disregarded - interaction between the immune system and cancer.

   The Emerging Science

National Cancer Institute. Immunotherapy Agent Workshop Proceedings. 2007.

This report from a 2007 workshop documents the emerging science that led to today's game-changing
I-O therapies.

Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007;7:95-106.

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-64.

Pardoll D, Drake C. Immunotherapy earns its spot in the ranks of cancer therapy. J Exp Med. 2012;209(2):201-9.

These reviews summarize the rapid advances in the science of immune checkpoints, and provide the rationale for their clinical use as cancer therapy.

   Into the Clinic

Topalian SL, Hodi FS, Brahmer JR, et al. Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. N Engl J Med. 2012;366:2443-54.

Brahmer JR, Tykodi SS, Chow LQM, et al. Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer. N Engl J Med. 2012;366:2455-65.

These back-to-back, landmark papers published in The New England Journal of Medicine report the very promising initial results of phase I clinical trials with monoclonal antibody inhibitors of PD-1 (now Opdivo) and its ligand, PD-L1. Dozens of clinical trial reports have followed, associated with regulatory approvals for a growing array of agents in an expanding range of tumor types.  

Postow MA, Callahan MK, Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol. 2015;33:1974-82.

An updated review of the basic and clinical science supporting the therapeutic use of immune checkpoint inhibitors in multiple solid and liquid tumors.

Topalian SL. Targeting Immune Checkpoints in Cancer Therapy. JAMA. Published online September 8, 2017: E1-2.

A succinct review of the current status of clinical I-O and the strategies under investigation for further improving outcomes.

   The CAR T Approach to I-O

National Cancer Institute. CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers. Accessed September 2017.

A good-to-begin-with summary of CAR T technology and how it fits into the cancer immunotherapy landscape.

   The Human Immune System

Sompayrac, L. How the Immune System Works, 5th Ed. Wiley-Blackwell, 2015.

A thorough and highly accessible introduction to the human immune system for those wanting to gain a better understanding of the mechanisms underlying cancer immunotherapy.

   For Information About I-O Clinical Trials

Search here: www.clinicaltrials.gov