title: A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo.
abstract: Antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) are key elements of immunological rejection in transplantation as well as cancer immunotherapy. Most tumors, however, are not immunologically rejected because they have self antigens, which are not recognized as the foreigner by CTLs. In this study, we hypothesized that "foreignizing" tumor cells by delivering non-self foreign antigens into the tumors would result in rejection by foreign antigen-reactive CTLs. As the model system to foreignize the tumors, we prepared a polymeric conjugate consisting of hyaluronic acid as the CD44(+) tumor-targeting ligand and ovalbumin (OVA) as a foreign antigen. When the conjugate was treated with CD44(high) TC-1 tumor cells, it was effectively taken up and allowed for displaying of antigenic OVA257-264 peptide at MHC class I on the surface of the cells. In addition, the conjugate was effectively accumulated into tumor tissue after its systemic administration to mice which are immunized with a vaccine for a vaccinia virus expressing OVA to generate OVA257-264 specific CTLs, resulting in substantial inhibition of tumor growth. Overall, these results suggest that the polymeric conjugates bearing foreign antigens may be innovative and promising cancer immunotherapeutic agents by foreignizing tumor cells, leading to immunological rejection.
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Infection and Immunology, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: G
authors.initials: G
authors.lastname: Saravanakumar
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Infection and Immunology, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Noh
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Infection and Immunology, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Kwon-Ho
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Division of Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jhpark1@skku.edu.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Infection and Immunology, Korea University College of Medicine, Seoul 136-701, Republic of Korea. Electronic address: twkim0421@korea.ac.kr.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005547:Foreign Bodies / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology; D006820:Hyaluronic Acid; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy; D010047:Ovalbumin / Q000276:immunology; D011108:Polymers; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014018:Tissue Distribution; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D018960:Hyaluronan Receptors; D011108:Polymers; D006820:Hyaluronic Acid; D010047:Ovalbumin
keywords: Antigen delivery; Cancer immunotherapy; Foreignization; Hyaluronic acid; Polymeric conjugate