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

Raffaella Fontana, Marco Bregni, Arcadi Cipponi, Laura Raccosta, Cristina Rainelli, Daniela Maggioni, Francesca Lunghi, Fabio Ciceri, Sylvain Mukenge, Claudio Doglioni, Didier Colau, Pierre G. Coulie, Claudio Bordignon, Catia Traversari, Vincenzo Russo

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Abstract

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 de-layed-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.

Original languageEnglish
Pages (from-to)1651-1660
Number of pages10
JournalBlood
Volume113
Issue number8
DOIs
Publication statusPublished - Feb 19 2009

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Fontana, R., Bregni, M., Cipponi, A., Raccosta, L., Rainelli, C., Maggioni, D., Lunghi, F., Ciceri, F., Mukenge, S., Doglioni, C., Colau, D., Coulie, P. G., Bordignon, C., Traversari, C., & Russo, V. (2009). Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients. Blood, 113(8), 1651-1660. https://doi.org/10.1182/blood-2008-07-168666