In one of the most comprehensive peer-reviewed discussions on cancer vaccines and immunotherapeutics, a Special Focus in the journal Human Vaccines & Immunotherapeutics provides a critical view on cancer vaccines and a discussion on best approaches for the future. From firsthand accounts of principal investigators involved in numerous failed cancer vaccine programs, including Oncophage® and MVAX®, to commentary from world experts in cancer vaccine development, authors in the Special Focus recount the mistakes of the past and provide an critical lens into the future of cancer vaccines with a potential for success.
Of special consideration is the technological advancement in Second Generation DNA sequencing technology that has resulted in the vast amount of genetic data of tumor cells gathered over the past few years. According to authors in the Special Focus, these data confirm that the degree of antigenic heterogeneity of tumor cells has been greatly underestimated. Tumors, once thought to be made of homogeneous collections of cells, are actually comprised of cells that carry an extreme diversity of antigens, the molecular signatures that are responsible for triggering immune response against cancer. This influences the important area of Antigen Discovery, a major criteria of vaccine formulation.
“Due in large part to genomic sequencing data, it has become quite clear that cancer is a heterogeneous disease and thus cannot be treated by homogeneous therapies. Many past cancer vaccine programs were based on the false premise of tumor homogeneity,” said Michael G. Hanna, Jr., Ph.D., guest editor and contributor in the Special Focus series. “With all that we have learned at both the tumor genomic and immunotherapeutic levels, it is essential to reevaluate the antigen discovery process. The use of the patient’s own tumor is the purest means to obtain a robust tumor-specific immune response.”
The promise of triggering the immune system to engage a perpetual defense against resilient and hard-to-find cancer cells continues to prompt research. There are approximately 150 therapeutic cancer vaccines in clinical development. Despite past failures of cancer vaccines, new science continues to validate and support cancer vaccine technologies. In this Special Focus, authors outline weak clinical trial design, manufacturing issues relating to short shelf life and sterility of product, and failure to identify proper dose, schedule and route of administration among the key reasons why more cancer vaccines are not on the market today.
Ronald Ellis, Ph.D., Editor-in-Chief of Human Vaccines & Immunotherapeutics, said: “Despite the accumulation of sound science that continues to support cancer immunotherapy approaches, there are serious gaps in the cancer vaccine R&D pipeline. Some new cancer vaccine technologies that apply the lessons learned from many years of trials and tribulations are in late stages of clinical development and could lead to realization of the promise of cancer immunotherapy.”
The Special Focus appearing in the August 2012 issue includes an introduction, five original papers and a guest editorial. Selected experts include: David Berd, M.D. (DB Consultants; Wyncote, PA, USA), Mike Cusnir, M.D. (Mount Sinai Comprehensive Cancer Center; Miami Beach, FL, USA), Isaiah Fidler, Ph.D. (University of Texas MD Anderson Cancer Center, Houston, TX, USA), Michael G. Hanna, Jr., Ph.D. (Vaccinogen Inc, Frederick, MD, USA), and Dirk Reitsma, M.D., and Austin Combest, Pharm.D. (PPD, Wilmington, NC, USA). Guest Editors include: Alex Kudrin, M.D., Ph.D. (Consultant in Pharmaceuticals Medicine, London, UK) and Michael G. Hanna, Jr., Ph.D. (Vaccinogen Inc, Frederick, MD, USA). This is the first of two special sections in the Cancer Commentary Series, the second will appear in the September 2012 issue.
Human Vaccines & Immunotherapeutics, Landes Bioscience