Valerie L Herrmann1, Daniel E Wieland2, Daniel F Legler3, Valentin Wittmann2, Marcus Groettrup1,3. 1. Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany. 2. Department of Chemistry, University of Konstanz, Konstanz, Germany. 3. Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
Abstract
BACKGROUND: PLGA microsphere-based vaccination has been proven to be effective in immunotherapy of syngeneic model tumors in mice. The critical step for the translation to humans is the identification of immunogenic tumor antigens and potent vaccine formulations to overcome immune tolerance. METHODS: HLA-A*0201 transgenic mice were immunized with eight different human prostate cancer peptide antigens co-encapsulated with TLR ligands into PLGA microspheres and analyzed for antigen-specific and functional cytotoxic T lymphocyte responses. RESULTS: Only vaccination with STEAP1(262-270) peptide encapsulated in PLGA MS could effectively crossprime CTLs in vivo. These CTLs recognized STEAP1(262-270) /HLA-A*0201 complexes on human dendritic cells and prostate cancer cell lines and specifically lysed target cells in vivo. Vaccination with PLGA microspheres was much more potent than with incomplete Freund's adjuvant. CONCLUSIONS: Our data suggests that there exist great differences in the immunogenicity of human PCa peptide antigens despite comparable MHC class I binding characteristics. Immunogenic STEAP1(262-270) peptide encapsulated into PLGA microspheres however was able to induce vigorous and functional antigen-specific CTLs and therefore is a promising novel approach for immunotherapy against advanced stage prostate cancer.
BACKGROUND: PLGA microsphere-based vaccination has been proven to be effective in immunotherapy of syngeneic model tumors in mice. The critical step for the translation to humans is the identification of immunogenic tumor antigens and potent vaccine formulations to overcome immune tolerance. METHODS:HLA-A*0201 transgenic mice were immunized with eight different humanprostate cancer peptide antigens co-encapsulated with TLR ligands into PLGA microspheres and analyzed for antigen-specific and functional cytotoxic T lymphocyte responses. RESULTS: Only vaccination with STEAP1(262-270) peptide encapsulated in PLGA MS could effectively crossprime CTLs in vivo. These CTLs recognized STEAP1(262-270) /HLA-A*0201 complexes on human dendritic cells and prostate cancer cell lines and specifically lysed target cells in vivo. Vaccination with PLGA microspheres was much more potent than with incomplete Freund's adjuvant. CONCLUSIONS: Our data suggests that there exist great differences in the immunogenicity of human PCa peptide antigens despite comparable MHC class I binding characteristics. Immunogenic STEAP1(262-270) peptide encapsulated into PLGA microspheres however was able to induce vigorous and functional antigen-specific CTLs and therefore is a promising novel approach for immunotherapy against advanced stage prostate cancer.
Authors: Julia Koerner; Dennis Horvath; Valerie L Herrmann; Anna MacKerracher; Bruno Gander; Hideo Yagita; Jacques Rohayem; Marcus Groettrup Journal: Nat Commun Date: 2021-05-18 Impact factor: 14.919