TY - JOUR
T1 - Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients
AU - Nisticò, Paola
AU - Capone, Imerio
AU - Palermo, Belinda
AU - Bello, Duilia Del
AU - Ferraresi, Virginia
AU - Moschella, Federica
AU - Aricò, Eleonora
AU - Valentini, Mara
AU - Bracci, Laura
AU - Cognetti, Francesco
AU - Ciccarese, Mariangela
AU - Vercillo, Giuseppe
AU - Roselli, Mario
AU - Fossile, Emanuela
AU - Tosti, Maria Elena
AU - Wang, Ena
AU - Marincola, Francesco
AU - Imberti, Luisa
AU - Catricalà, Caterina
AU - Natali, Pier Giorgio
AU - Belardelli, Filippo
AU - Proietti, Enrico
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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 pro1of 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.
AB - 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 pro1of 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.
KW - Chemoimmunotherapy
KW - Dacarbazine
KW - Human melanoma
KW - Peptide vaccination
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U2 - 10.1002/ijc.23886
DO - 10.1002/ijc.23886
M3 - Article
C2 - 18839429
AN - SCOPUS:58149376993
VL - 124
SP - 130
EP - 139
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 1
ER -