A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo

Title
A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo
Authors
이영호윤홍열신정민G. Saravanakumar노경희송권호전주홍김동완이경미김광명권익찬박재형김태우
Issue Date
2015-02
Publisher
Journal of controlled release
Citation
VOL 199, 98-105
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 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.
URI
http://pubs.kist.re.kr/handle/201004/49346
ISSN
01683659
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KIST Publication > Article
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