title: T Cells as Antigen Carriers for Anti-tumor Vaccination.
abstract: The exploitation of the physiologic processing and presenting machinery of dendritic cells (DCs) by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. The approach developed by our group was based on the clinical observation that some patients treated with the infusion of donor lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies, after allogeneic hematopoietic stem cell transplantation, developed a T cell-mediated immune response specifically directed against the HSV-TK gene product.We demonstrated that lymphocytes genetically modified to express HSV-TK as well as self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of TRP-2-transduced lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice by cross-presentation of the antigen mediated by the CD11c(+)CD8a(+) DCs subset. A similar approach was applied in a clinical setting. Ten patients affected by MAGE-3(+) metastatic melanoma were treated with autologous lymphocytes retrovirally transduced to express the MAGE-3 tumor antigen. In three patients, the treatment led to the increase of MAGE-3 specific CD8+ and CD4+ effectors and the development of long-term memory, which ultimately correlated with a favorable clinical outcome. Transduced lymphocytes represent an efficient way for in vivo loading of tumor-associated antigens of DCs.
authors.affiliation: MolMed SpA, Via Olgettina, 58, 20132, Milano, Italy. catia.traversari@molmed.com.
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
authors.affiliation: Cancer Gene Therapy Unit, IRCCS San Raffaele Hospital, Milano, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology*; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins
keywords: Active immunotherapy; Cross-presentation; Tumor antigens