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Current Developments in Cancer Vaccines and Cellular Immunotherapy

Antoni Ribas, Lisa H. Butterfield, John A. Glaspy, James S. Economou

From the Divisions of Hematology-Oncology, Departments of Medicine, Surgical-Oncology, Surgery, and Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA.

Address reprint requests to Antoni Ribas, MD, Division of Hematology-Oncology, 11-934 Factor Bldg, UCLA Medical Center, 10833 Le Conte Avenue, Los Angeles, CA 90095-1782. email: aribas{at}mednet.ucla.edu.

This article reviews the immunologic basis of clinical trials that test means of tumor antigen recognition and immune activation, with the goal to provide the clinician with a mechanistic understanding of ongoing cancer vaccine and cellular immunotherapy clinical trials. Multiple novel immunotherapy strategies have reached the stage of testing in clinical trials that were accelerated by recent advances in the characterization of tumor antigens and by a more precise knowledge of the regulation of cell-mediated immune responses. The key steps in the generation of an immune response to cancer cells include loading of tumor antigens onto antigen-presenting cells in vitro or in vivo, presenting antigen in the appropriate immune stimulatory environment, activating cytotoxic lymphocytes, and blocking autoregulatory control mechanisms. This knowledge has opened the door to antigen-specific immunization for cancer using tumor-derived proteins or RNA, or synthetically generated peptide epitopes, RNA, or DNA. The critical step of antigen presentation has been facilitated by the coadministration of powerful immunologic adjuvants, the provision of costimulatory molecules and immune stimulatory cytokines, and the ability to culture dendritic cells. Advances in the understanding of the nature of tumor antigens and their optimal presentation, and in the regulatory mechanisms that govern the immune system, have provided multiple novel immunotherapy intervention strategies that are being tested in clinical trials.

Supported by National Institutes of Health/National Cancer Institute RO1 CA 77623, RO1 CA 79976, T32 CA75956, K12 CA 79605, and the Monkarsh Fund, Naify Fund, and the Stacy and Evelyn Kesselman Research Fund (all to J.S.E.). A.R. is a recipient of a Career Development Award from the American Society of Clinical Oncology, the Richard Barasch Seed Grant Award, a Career Development Award from Stop Cancer, and K23 CA93376.

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