A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo

Young Ho Lee, Hong Yeol Yoon, Jung Min Shin, G. Saravanakumar, Kyung Hee Noh, Kwon Ho Song, Ju Hong Jeon, Dong Wan Kim, Kyung-Mi Lee, Kwang Meyung Kim, Ick Chan Kwon, Jae Hyung Park, Tae Woo Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)98-105
Number of pages8
JournalJournal of Controlled Release
Volume199
DOIs
Publication statusPublished - 2015 Feb 10

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Immunotherapy
Cytotoxic T-Lymphocytes
Neoplasms
Ovalbumin
Antigens
CD8 Antigens
Vaccinia virus
Autoantigens
Graft Rejection
Neoplasm Antigens
Hyaluronic Acid
Vaccines
Ligands
Peptides
Growth

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo. / 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, Kwang Meyung; Kwon, Ick Chan; Park, Jae Hyung; Kim, Tae Woo.

In: Journal of Controlled Release, Vol. 199, 10.02.2015, p. 98-105.

Research output: Contribution to journalArticle

Lee, YH, Yoon, HY, Shin, JM, Saravanakumar, G, Noh, KH, Song, KH, Jeon, JH, Kim, DW, Lee, K-M, Kim, KM, Kwon, IC, Park, JH & Kim, TW 2015, 'A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo', Journal of Controlled Release, vol. 199, pp. 98-105. https://doi.org/10.1016/j.jconrel.2014.12.007
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, Kwang Meyung ; Kwon, Ick Chan ; Park, Jae Hyung ; Kim, Tae Woo. / A polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo. In: Journal of Controlled Release. 2015 ; Vol. 199. pp. 98-105.
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