Diversification of TCR repertoire in melanoma patients treated with chemotherapy before peptides-vaccination (41.19)

Abstract

Abstract Combining chemotherapy and immunotherapy is an attractive antitumor strategy. Recently we have reported that the administration of dacarbazine (DTIC) one day before peptide-vaccination in disease-free melanoma patients induced an increase of peptide-specific effector-memory CD8+ lymphocytes. To investigate the functional differences between anti-Melan-A CD8+ T cell response elicited by vaccination alone (Arm 1) or by chemotherapy plus vaccination (Arm 2), we generated T cell clones from 5 patients of both Arms, before and after the treatments. A significant enhancement of tumor lytic activity of Melan-A+ clones generated by patients of Arm 2 after the treatment was observed, whereas no significant differences of tumor recognition efficiency were evident among the two arms before treatment. Ninety-six sequences were obtained and 47 clonotypes with different CDR3 regions were observed. A progressive enhancement of TCR repertoire diversity was found only in patients treated with DTIC before vaccination, whereas patients treated with vaccine alone showed a reduction of TCR repertoire diversity accompanied by a reduction of tumor lytic activity in one patient. These results suggest that a diverse Melan-A-specific T cell repertoire occurs in melanoma patients treated with DTIC plus vaccination, which may offer a new clinically advantageous anti-tumor strategy.