A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo

• Published in: Journal of controlled release Vol. 199; pp. 98 - 105
• Main Authors: Lee, Young-Ho, Yoon, Hong Yeol, Shin, Jung Min, Saravanakumar, G., Noh, Kyung Hee, Song, Kwon-Ho, Jeon, Ju-Hong, Kim, Dong-Wan, Lee, Kyung-Mi, Kim, Kwangmeyung, Kwon, Ick Chan, Park, Jae Hyung, Kim, Tae Woo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.02.2015
• Subjects: Animals; Antigen delivery; Antigen Presentation; antigens; Apoptosis - drug effects; Cancer immunotherapy; cytotoxic T-lymphocytes; Drug Delivery Systems - methods; Female; Foreign Bodies - immunology; Foreignization; Genes, MHC Class I - immunology; Hyaluronan Receptors - immunology; Hyaluronic Acid; immunotherapy; Immunotherapy - methods; ligands; major histocompatibility complex; Mice; Mice, Inbred C57BL; neoplasm cells; neoplasms; Neoplasms, Experimental - therapy; ovalbumin; Ovalbumin - immunology; Polymeric conjugate; Polymers; T-Lymphocytes, Cytotoxic - immunology; Tissue Distribution; vaccines; Vaccinia virus; Vaccinia virus - immunology; Cancer immunotherapy; Hyaluronic acid; Antigen delivery; Polymeric conjugate; Foreignization
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2014.12.007

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 CD44high 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. Targeted delivery of foreign antigen to the tumor cells using the polymeric conjugate allows for immunological rejection of the tumor. [Display omitted]