High efficiency of low-affinity epitopes in cancer therapy reported.

2004 APR 21 - (NewsRx.com & NewsRx.net) -- Scientists report the high vaccination efficiency of low-affinity epitopes in antitumor immunotherapy.

"Most of the human tumor-associated antigens (TAAs) characterized thus far are derived from non-mutated 'self'-proteins. Numerous strategies have been developed to break tolerance to TAAs, combining various forms of antigens with different vectors and adjuvants. However, no study has yet determined how to select epitopes within a given TAA to induce the highest antitumor effector response," researchers in France report.

"We addressed this question by evaluating in HLA-A*0201-transgenic HHD mice the antitumor vaccination efficacy of high- and low-affinity epitopes from the naturally expressed murine telomerase reverse transcriptase (mTERT)," said David-Alexandre Gross at the Centre National de la Recherche Scientifique and collaborators in France. "Immunity against low-affinity epitopes was induced with heteroclitical variants. We show here that the CTL repertoire against high-affinity epitopes is partially tolerized, while that against low-affinity epitopes is composed of frequent CTLs with high avidity. The high-affinity p797 and p545 mTERT epitopes are not able to protect mice from a lethal challenge with the mTERT-expressing EL4-HHD tumor."