Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients
Corresponding Author
Paola Nisticò
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Fax: +39-06-52662600
Paola Nisticò, Laboratory of Immunology, Regina Elena Cancer Institute, Via delle Messi d'oro 156, 00158 Rome, Italy
Enrico Proietti, Department of Cell Biology and Neurosciences, Viale Regina Elena 299, 00161 Rome, Italy
Search for more papers by this authorImerio Capone
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorBelinda Palermo
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorDuilia Del Bello
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorVirginia Ferraresi
Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorFederica Moschella
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorEleonora Aricò
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorMara Valentini
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorLaura Bracci
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorFrancesco Cognetti
Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorMariangela Ciccarese
Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorGiuseppe Vercillo
Department of Pathology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorMario Roselli
Medical Oncology AFA Surgery, University of Rome “Tor Vergata”, Rome, Italy
Search for more papers by this authorEmanuela Fossile
Medical Oncology AFA Surgery, University of Rome “Tor Vergata”, Rome, Italy
Search for more papers by this authorMaria Elena Tosti
National Center for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorEna Wang
Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD
Search for more papers by this authorFrancesco Marincola
Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD
Search for more papers by this authorLuisa Imberti
Diagnostic Department, Spedali Civili di Brescia, Brescia, Italy
Search for more papers by this authorCaterina Catricalà
Department of Dermatology-Oncology, S. Gallicano Dermatological Institute, Rome, Italy
Search for more papers by this authorPier Giorgio Natali
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorFilippo Belardelli
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorCorresponding Author
Enrico Proietti
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Fax: +39-06-49903641
Paola Nisticò, Laboratory of Immunology, Regina Elena Cancer Institute, Via delle Messi d'oro 156, 00158 Rome, Italy
Enrico Proietti, Department of Cell Biology and Neurosciences, Viale Regina Elena 299, 00161 Rome, Italy
Search for more papers by this authorCorresponding Author
Paola Nisticò
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Fax: +39-06-52662600
Paola Nisticò, Laboratory of Immunology, Regina Elena Cancer Institute, Via delle Messi d'oro 156, 00158 Rome, Italy
Enrico Proietti, Department of Cell Biology and Neurosciences, Viale Regina Elena 299, 00161 Rome, Italy
Search for more papers by this authorImerio Capone
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorBelinda Palermo
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorDuilia Del Bello
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorVirginia Ferraresi
Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorFederica Moschella
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorEleonora Aricò
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorMara Valentini
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorLaura Bracci
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorFrancesco Cognetti
Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorMariangela Ciccarese
Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorGiuseppe Vercillo
Department of Pathology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorMario Roselli
Medical Oncology AFA Surgery, University of Rome “Tor Vergata”, Rome, Italy
Search for more papers by this authorEmanuela Fossile
Medical Oncology AFA Surgery, University of Rome “Tor Vergata”, Rome, Italy
Search for more papers by this authorMaria Elena Tosti
National Center for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorEna Wang
Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD
Search for more papers by this authorFrancesco Marincola
Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD
Search for more papers by this authorLuisa Imberti
Diagnostic Department, Spedali Civili di Brescia, Brescia, Italy
Search for more papers by this authorCaterina Catricalà
Department of Dermatology-Oncology, S. Gallicano Dermatological Institute, Rome, Italy
Search for more papers by this authorPier Giorgio Natali
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy
Search for more papers by this authorFilippo Belardelli
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Search for more papers by this authorCorresponding Author
Enrico Proietti
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Fax: +39-06-49903641
Paola Nisticò, Laboratory of Immunology, Regina Elena Cancer Institute, Via delle Messi d'oro 156, 00158 Rome, Italy
Enrico Proietti, Department of Cell Biology and Neurosciences, Viale Regina Elena 299, 00161 Rome, Italy
Search for more papers by this authorAbstract
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.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IJC_23886_sm_suppinfoTable.doc354.5 KB | Supplementary Table. List of the genes modulated by DTIC |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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