title: Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells.
abstract: Vaccination with dendritic cells (DCs) pulsed with antigenic peptides derived from various tumor antigens has great, but as yet significantly unrealized, potential in cancer treatment. Here, we describe a strategy for prolonged presentation of an MHC class I-restricted self-peptide on DCs through linkage of it to a cell penetrating peptide (CPP). DCs loaded with a peptide derived from tyrosinase-related protein 2 (TRP2) covalently linked to a CPP1 sequence retained full capacity to stimulate T cells for at least 24 h, completely protected immunized mice from subsequent tumor challenge, and significantly inhibited lung metastases in a 3-day tumor model. DCs pulsed with TRP2 alone failed to provide any of these protections. In addition, we demonstrate that both CD4+ and CD8+ T cells were required for potent antitumor immunity. This CPP-based approach may be generally applicable to enhance the efficacy of DC-based peptide vaccines against cancer and other diseases.
authors.affiliation: The Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. rongfuw@bcm.tmc.edu
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D010455:Peptides / Q000737:chemistry; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D010455:Peptides