A common drawback of many cancer immunotherapies,including immune checkpoint blockade,is their reliance on the expression of immunogenic tumor antigens by cancer cells for immune recognition and clearance,which limits...A common drawback of many cancer immunotherapies,including immune checkpoint blockade,is their reliance on the expression of immunogenic tumor antigens by cancer cells for immune recognition and clearance,which limits their efficacy against cancers with weak antigenicity.1 To overcome this obstacle,we and others have explored strategies to harness the immune responses against nontumor antigens and redirect those immune responses to target tumor cells.2,3,4,5 In particular,we have pioneered a therapeutic strategy fusing tumor-targeting proteins with known antigenic peptide epitopes not naturally expressed by tumor cells,which are flanked by peptide sequences that can be recognized and cleaved by proteases overexpressed in most cancers.2,3 This strategy facilitates the targeted delivery of immunogenic peptides into tumor foci,the release of immunogenic peptides into the tumor microenvironment(TME)via tumor protease cleavage,and subsequent loading of these peptides onto major histocompatibility complex class 1(MHC-I)on the tumor cell surface,allowing the recognition of coated tumor cells by the respective peptide-specific cytotoxic CD8+T lymphocytes(CTLs)for elimination.展开更多
基金supported by NIH/NCI P50 CA098252,NIH/NCI R21CA234516 and NIH/NCI R01 CA233486supported by the KU Research Professor Program of Konkuk University.
文摘A common drawback of many cancer immunotherapies,including immune checkpoint blockade,is their reliance on the expression of immunogenic tumor antigens by cancer cells for immune recognition and clearance,which limits their efficacy against cancers with weak antigenicity.1 To overcome this obstacle,we and others have explored strategies to harness the immune responses against nontumor antigens and redirect those immune responses to target tumor cells.2,3,4,5 In particular,we have pioneered a therapeutic strategy fusing tumor-targeting proteins with known antigenic peptide epitopes not naturally expressed by tumor cells,which are flanked by peptide sequences that can be recognized and cleaved by proteases overexpressed in most cancers.2,3 This strategy facilitates the targeted delivery of immunogenic peptides into tumor foci,the release of immunogenic peptides into the tumor microenvironment(TME)via tumor protease cleavage,and subsequent loading of these peptides onto major histocompatibility complex class 1(MHC-I)on the tumor cell surface,allowing the recognition of coated tumor cells by the respective peptide-specific cytotoxic CD8+T lymphocytes(CTLs)for elimination.
