Premium
Chemotherapy enhances vaccine‐induced antitumor immunity in melanoma patients
Author(s) -
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
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23886
Subject(s) - medicine , dacarbazine , immune system , immunology , cd8 , melanoma , immunotherapy , vaccination , antigen , chemotherapy , peripheral blood mononuclear cell , human leukocyte antigen , t cell , cancer , cancer research , biology , in vitro , biochemistry
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.