Chemotherapy enhances vaccine‐induced antitumor immunity in melanoma patients

• Published in: International journal of cancer 2009-01, Vol.124 (1), p.130-139
• Main Authors: Nisticò, Paola, Capone, Imerio, Palermo, Belinda, Del Bello, Duilia, Ferraresi, Virginia, Moschella, Federica, Aricò, Eleonora, Valentini, Mara, Bracci, Laura, Cognetti, Francesco, Ciccarese, Mariangela, Vercillo, Giuseppe, Roselli, Mario, Fossile, Emanuela, Tosti, Maria Elena, Wang, Ena, Marincola, Francesco, Imberti, Luisa, Catricalà, Caterina, Natali, Pier Giorgio, Belardelli, Filippo, Proietti, Enrico
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cancer Vaccines - therapeutic use; CD8-Positive T-Lymphocytes - metabolism; chemoimmunotherapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); dacarbazine; Female; human melanoma; Humans; Immunotherapy - methods; Interferon-alpha - metabolism; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Melanoma - drug therapy; Melanoma - immunology; Middle Aged; Neoplasm Metastasis; peptide vaccination; Pharmacology. Drug treatments; Pilot Projects; Treatment Outcome; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23886

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.