Exosome Targeting of Tumor Antigens Expressed by Cancer Vaccines Can Improve Antigen Immunogenicity and Therapeutic Efficacy

摘要: MVA-BN®-PRO is a candidate immunotherapy product for the treatment of prostate cancer. It encodes two tumor-associated antigens (TAA), prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP), derived from highly attenuated Modified Vaccinia Ankara virus stock known as MVA-BN®. Past work has shown that immunogenicity can be improved by targeting their localization to exosomes, which are small, 50-100 nm diameter vesicles secreted most cell types. Exosome achieved fusing C1C2 domain Lactadherin protein. To test if exosome-targeting would improve PSA PAP, additional versions were produced, either (MVA-BN®-PSA-C1C2) or PAP (MVA-BN®-PAP-C1C2) while leaving second transgene untargeted. Treatment mice with MVA-BN®-PAP-C1C2 led striking increase in immune response against PAP. Anti-PAP antibody titers developed more rapidly reached levels 10 100-fold higher than treated MVA-BN®-PRO. Furthermore, increased frequency PAP-specific T cells 5-fold compared These improvements translated into greater tumor rejection PAP-expressing solid model. Likewise, MVA-BN®-PSA-C1C2 antigenicity MVA-BN®-PRO, resulted trend anti-tumor efficacy PSA-expressing experiments confirm exosomes viable approach improving therapeutic potential humans.