Cancer vaccine using low affinity epitopes proves successful in mice

Antitumor immunotherapy is a challenging endeavor since most human tumor–associated antigens are nonmutated self-proteins expressed on normal tissues. The ideal vaccination approach requires self-tolerance while eliciting an effective antitumor response. In an effort to design the ideal vaccine, David-Alexandre Gross and colleagues from Institut Gustave Roussy, France, examined epitopes (parts of antigen molecules) derived from murine telomerase reverse transcriptase (mTERT) – an enzyme expressed in more than 80% of human tumors – as potential anticancer vaccines. In the February 2 issue of the Journal of Clinical Investigation they report that epitopes with a low affinity for HLA class I molecules, molecules which bind and present antigens to T cells for killing – could be modified to generate an immune response against the tumor without stimulating an immune response against self. Mice vaccinated with the modified low-affinity epitopes maintained tumor immunity, while mice vaccinated with high-affinity epitopes died after challenge with tumor cells. These studies highlight the importance of rational epitope selection for effective cancer vaccines.

TITLE: High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy

AUTHOR CONTACT:
David-Alexandre Gross
Institut Gustave Roussy, Cedex, France.
Phone: 33-1-69-47-25-77
Fax: 33-1-60-77-86-98
E-mail: gross@genethon.fr

View the PDF of this article at: http://www.jci.org/cgi/content/full/113/3/425

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