Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients

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 NataliFilippo Belardelli, Enrico Proietti

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77 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)130-139
Number of pages10
JournalInternational Journal of Cancer
Volume124
Issue number1
DOIs
Publication statusPublished - 1 Jan 2009

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Keywords

  • Chemoimmunotherapy
  • Dacarbazine
  • Human melanoma
  • Peptide vaccination

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nisticò, P., Capone, I., Palermo, B., Bello, D. D., Ferraresi, V., Moschella, F., Aricò, E., Valentini, M., Bracci, L., Cognetti, F., Ciccarese, M., Vercillo, G., Roselli, M., Fossile, E., Tosti, M. E., Wang, E., Marincola, F., Imberti, L., Catricalà, C., ... Proietti, E. (2009). Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients. International Journal of Cancer, 124(1), 130-139. https://doi.org/10.1002/ijc.23886