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 2024-01-20T07:34:20Z 2024-01-20T07:34:20Z 2021-09-05 2015-02-10 0168-3659 https://pubs.kist.re.kr/handle/201004/125768 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 OVA(257-264) 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 OVA(257-264) 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. (C) 2014 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo Article 10.1016/j.jconrel.2014.12.007 1 JOURNAL OF CONTROLLED RELEASE, v.199, pp.98 - 105 JOURNAL OF CONTROLLED RELEASE 199 98 105 scie scopus 000348456800011 2-s2.0-84949114933 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article Polymeric conjugate Cancer immunotherapy Antigen delivery Hyaluronic acid Foreignization