title: Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients.
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 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.
authors.affiliation: Cancer Gene Therapy Unit, Cancer Immunotherapy and Gene Therapy Program, Department of Oncology, Scientific Institute San Raffaele, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fontana
authors.forename: Marco
authors.initials: M
authors.lastname: Bregni
authors.forename: Arcadi
authors.initials: A
authors.lastname: Cipponi
authors.forename: Laura
authors.initials: L
authors.lastname: Raccosta
authors.forename: Cristina
authors.initials: C
authors.lastname: Rainelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Maggioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunghi
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mukenge
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Didier
authors.initials: D
authors.lastname: Colau
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Coulie
authors.forename: Claudio
authors.initials: C
authors.lastname: Bordignon
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D019556:COS Cells; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology*; D009367:Neoplasm Staging; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D013937:Thymidine Kinase