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A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo.

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
Source :
Journal of Controlled Release. Feb2015, Vol. 199, p98-105. 8p.
Publication Year :
2015

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 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01683659
Volume :
199
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
100680863
Full Text :
https://doi.org/10.1016/j.jconrel.2014.12.007