Developing immunotherapeutic approaches to treat individuals with cancer is an area of intensive investigation. One such approach being developed is the generation of cancer vaccines containing peptides that mimic tumor antigens (known as mimotopes) to induce potent tumor-specific T cell responses. However, previous studies have indicated that the magnitude of a tumor antigen-specific T cell response in vitro does not always correlate with tumor regression in vivo.
Now, in a study appearing online on August 24 in advance of publication in the September print issue of the Journal of Clinical Investigation, Jill Slansky and colleagues from the University of Colorado have shown that mice vaccinated with mimotopes that induce in vitro T cell responses of intermediate magnitude are protected against tumor growth. By contrast, mimotopes that induce in vitro T cell responses of high magnitude do not protect mice from tumor growth. Both types of mimotope caused T cells to infiltrate the tumors, but only the T cells activated by mimotopes inducing in vitro T cell responses of intermediate magnitude produced the soluble factor interferon-gamma, which is important for effective tumor-specific T cell responses. This study has important implications for the further development of cancer vaccines containing mimotopes, as many current studies have used the magnitude of a tumor-specific T cell response to identify the best mimotope for the vaccine.
TITLE: Relating TCR-peptide-MHC affinity to immunogenicity for the design of tumor vaccines
Jill E. Slansky
University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA.
Phone: 303-398-1887; Fax: 303-398-1396; E-mail: Jill.Slansky@UCHSC.edu.
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