Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients

✍ Scribed by Paola Nisticò; Imerio Capone; Belinda Palermo; Duilia Del Bello; Virginia Ferraresi; Federica Moschella; Eleonora Aricò; Mara Valentini; Laura Bracci; Francesco Cognetti; Mariangela Ciccarese; Giuseppe Vercillo; Mario Roselli; Emanuela Fossile; Maria Elena Tosti; Ena Wang; Francesco Marincola; Luisa Imberti; Caterina Catricalà; Pier Giorgio Natali; Filippo Belardelli; Enrico Proietti

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: French
• Weight: 1019 KB
• Volume: 124
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23886

✦ Synopsis

Abstract

Combination of chemotherapy with cancer vaccines is currently regarded as a potentially valuable therapeutic approach for the treatment of some metastatic tumors, but optimal modalities remain unknown. We designed a phase I/II pilot study for evaluating the effects of dacarbazine (DTIC) on the immune response in HLA‐A2^+^ disease‐free melanoma patients who received anticancer vaccination 1 day following chemotherapy (800 mg/mq i.v.). The vaccine, consisting of a combination of HLA‐A2 restricted melanoma antigen A (Melan‐A/MART‐1) and gp100 analog peptides (250 μg each, i.d.), was administered in combination or not with DTIC to 2 patient groups. The combined treatment is nontoxic. The comparative immune monitoring demonstrates that patients receiving DTIC 1 day before the vaccination have a significantly improved long‐lasting memory CD8^+^ T cell response. Of relevance, these CD8^+^ T cells recognize and lyse HLA‐A2^+^/Melan‐A^+^ tumor cell lines. Global transcriptional analysis of peripheral blood mononuclear cells (PBMC) revealed a DTIC‐induced activation of genes involved in cytokine production, leukocyte activation, immune response and cell motility that can favorably condition tumor antigen‐specific CD8^+^ T cell responses. This study represents a proof in humans of a chemotherapy‐induced enhancement of CD8^+^ memory T cell response to cancer vaccines, which opens new opportunities to design novel effective combined therapies improving cancer vaccination effectiveness. © 2008 Wiley‐Liss, Inc.