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 Natali & 2 others Filippo Belardelli, Enrico Proietti

Research output: Contribution to journalArticle

76 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
Externally publishedYes

Fingerprint

Dacarbazine
Immunity
Melanoma
HLA-A2 Antigen
Vaccines
Drug Therapy
MART-1 Antigen
T-Lymphocytes
Cancer Vaccines
Vaccination
Melanoma-Specific Antigens
Immunologic Monitoring
Neoplasm Antigens
Therapeutics
Combination Drug Therapy
Tumor Cell Line
Transcriptional Activation
Cell Movement
Blood Cells
Neoplasms

Keywords

  • Chemoimmunotherapy
  • Dacarbazine
  • Human melanoma
  • Peptide vaccination

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Nisticò, P., Capone, I., Palermo, B., Bello, D. D., Ferraresi, V., Moschella, F., ... 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

Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients. / Nisticò, Paola; Capone, Imerio; Palermo, Belinda; Bello, Duilia Del; 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.

In: International Journal of Cancer, Vol. 124, No. 1, 01.01.2009, p. 130-139.

Research output: Contribution to journalArticle

Nisticò, P, Capone, I, Palermo, B, Bello, DD, Ferraresi, V, Moschella, F, Aricò, E, Valentini, M, Bracci, L, Cognetti, F, Ciccarese, M, Vercillo, G, Roselli, M, Fossile, E, Tosti, ME, Wang, E, Marincola, F, Imberti, L, Catricalà, C, Natali, PG, Belardelli, F & Proietti, E 2009, 'Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients', International Journal of Cancer, vol. 124, no. 1, pp. 130-139. https://doi.org/10.1002/ijc.23886
Nisticò P, Capone I, Palermo B, Bello DD, Ferraresi V, Moschella F et al. Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients. International Journal of Cancer. 2009 Jan 1;124(1):130-139. https://doi.org/10.1002/ijc.23886
Nisticò, Paola ; Capone, Imerio ; Palermo, Belinda ; Bello, Duilia Del ; 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. / Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients. In: International Journal of Cancer. 2009 ; Vol. 124, No. 1. pp. 130-139.
@article{d604cd24a53e4e6e9ff264a8fd988c47,
title = "Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients",
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.",
keywords = "Chemoimmunotherapy, Dacarbazine, Human melanoma, Peptide vaccination",
author = "Paola Nistic{\`o} and Imerio Capone and Belinda Palermo and Bello, {Duilia Del} and Virginia Ferraresi and Federica Moschella and Eleonora Aric{\`o} and Mara Valentini and Laura Bracci and Francesco Cognetti and Mariangela Ciccarese and Giuseppe Vercillo and Mario Roselli and Emanuela Fossile and Tosti, {Maria Elena} and Ena Wang and Francesco Marincola and Luisa Imberti and Caterina Catrical{\`a} and Natali, {Pier Giorgio} and Filippo Belardelli and Enrico Proietti",
year = "2009",
month = "1",
day = "1",
doi = "10.1002/ijc.23886",
language = "English",
volume = "124",
pages = "130--139",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=58149376993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149376993&partnerID=8YFLogxK

U2 - 10.1002/ijc.23886

DO - 10.1002/ijc.23886

M3 - Article

VL - 124

SP - 130

EP - 139

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 1

ER -