Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients

Dendritic cell (DC) targeting in vivo has recently been shown to confer strong and protective cytotoxic T lymphocyte (CTL)-based immunity in tumor murine models. Our group has recently demonstrated in preclinical models that the infusion of genetically modified lymphocytes (GMLs) expressing the self...

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Published in:Blood Vol. 113; no. 8; p. 1651
Main Authors: Fontana, Raffaella, Bregni, Marco, Cipponi, Arcadi, Raccosta, Laura, Rainelli, Cristina, Maggioni, Daniela, Lunghi, Francesca, Ciceri, Fabio, Mukenge, Sylvain, Doglioni, Claudio, Colau, Didier, Coulie, Pierre G, Bordignon, Claudio, Traversari, Catia, Russo, Vincenzo
Format: Journal Article
Language:English
Published: United States 19.02.2009
Subjects:
Adoptive Transfer
Animals
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Cancer Vaccines - administration & dosage
Cancer Vaccines - adverse effects
Cell Line, Tumor
Chlorocebus aethiops
COS Cells
Genetic Therapy - methods
Humans
Hypersensitivity, Delayed - immunology
Melanoma - immunology
Melanoma - pathology
Melanoma - therapy
Neoplasm Proteins - genetics
Neoplasm Proteins - immunology
Neoplasm Staging
Pilot Projects
Skin Neoplasms - immunology
Skin Neoplasms - pathology
Skin Neoplasms - therapy
T-Lymphocytes - cytology
T-Lymphocytes - physiology
T-Lymphocytes - transplantation
Thymidine Kinase - genetics
Thymidine Kinase - immunology
Transfection
ISSN:1528-0020, 1528-0020
Online Access:Get more information
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Summary:Dendritic cell (DC) targeting in vivo has recently been shown to confer strong and protective cytotoxic T lymphocyte (CTL)-based immunity in tumor murine models. Our group has recently demonstrated in preclinical models that the infusion of genetically modified lymphocytes (GMLs) expressing the self/tumor antigen TRP-2 is able to elicit functional TRP-2-specific effectors with antitumor activity by targeting DCs in vivo. Here we have analyzed vaccine- and tumor-specific immune responses of 10 melanoma patients treated with autologous GMLs expressing the cancer germline gene MAGE-A3. Three of 10 patients treated with MAGE-A3-GML showed an increase of circulating anti-MAGE-A3 T cells, and developed skin delayed-type hypersensitivity to MAGE-A3. Interestingly, in 2 of these patients, with progressive and measurable tumors at study entry, anti-MAGE-A3 T cells were detected not only in the blood but also within tumors resected after vaccination. These results demonstrate that the infusion of MAGE-A3-GML elicits antitumor T cells, which are capable of trafficking to inflamed tissues and of infiltrating tumors. Clinical studies on a larger group of patients are needed to evaluate the clinical efficacy of such a strategy.
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ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2008-07-168666