title: CD4 T-cells transduced with CD80 and 4-1BBL mRNA induce long-term CD8 T-cell responses resulting in potent antitumor effects.
abstract: Therapeutic cancer vaccines are an attractive alternative to conventional therapies to treat malignant tumors, and more importantly, to prevent recurrence after primary therapy. However, the availability of professional antigen-presenting cells (APCs) has been restricted by difficulties encountered in obtaining sufficient professional APCs for clinical use. We have prepared an alternative cellular vaccine with CD4 T-cells that can be expanded easily to yield a pure and homogeneous population in vitro. To enhance their potency as a therapeutic vaccine, in vitro expanded CD4 T-cells were transfected with RNAs encoding the costimulatory ligands CD80, 4-1BBL, or both (CD80-T, 4-1BBL-T, and CD80/4-1BBL-T-cells, respectively). We observed augmented cell vitality in CD80/4-1BBL-T-cells in vitro and in vivo. Significant CD8 T-cell responses eliciting in vivo proliferation and cytotoxicity were obtained with CD80/4-1BBL-T-cell vaccination compared to CD80-T and 4-1BBL-T-cell vaccinations. In contrast, β2m-deficient CD80/4-1BBL-T-cells were not as effective as wile-type CD80/4-1BBL-T-cells in priming CD8 T-cells. Furthermore, CD80/4-1BBL-T-cell immunization resulted in curing established EG7 tumors, resulting in the generation of memory CD8 T-cell responses, and elicited therapeutic antitumor responses against B16 melanoma. These results suggest that CD4 T-cells endowed with costimulatory ligands allow the design of effective vaccination strategies against cancer.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Park
authors.affiliation: Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Sohn
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea. Electronic address: hyun.cho@catholic.ac.kr.
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea. Electronic address: kimtg@catholic.ac.kr.
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D012333:RNA, Messenger; D014161:Transduction, Genetic; D016896:Treatment Outcome
chemical_list: D053330:4-1BB Ligand; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D012333:RNA, Messenger
keywords: CD4 T-cells; Cancer vaccine; Costimulatory ligand; Tumor immunity