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/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.
Fontana
Raffaella
R
Cancer Gene Therapy Unit, Cancer Immunotherapy and Gene Therapy Program, Department of Oncology, Scientific Institute San Raffaele, Milan, Italy.
Bregni
Marco
M
Cipponi
Arcadi
A
Raccosta
Laura
L
Rainelli
Cristina
C
Maggioni
Daniela
D
Lunghi
Francesca
F
Ciceri
Fabio
F
Mukenge
Sylvain
S
Doglioni
Claudio
C
Colau
Didier
D
Coulie
Pierre G
PG
Bordignon
Claudio
C
Traversari
Catia
C
Russo
Vincenzo
V
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D013937:Thymidine Kinase