A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy

Jung Min Shin, Se Jin Oh, Seunglee Kwon, V. G. Deepagan, Minchang Lee, Seok Ho Song, Hyo Jung Lee, Suyeon Kim, Kwon Ho Song, Tae Woo Kim, Jae Hyung Park

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen. The MMP9-cleavable linker was introduced between PEG and the HA backbone to facilitate the detachment of the PEG corona from the conjugate at the tumor site. From the in vitro cellular uptake study, it was revealed that the conjugate was effectively taken up by the CD44-expressing TC-1 cancer cells in the presence of MMP9 via receptor-mediated endocytosis. When the conjugate was systemically administered into the tumor-bearing mice with endogenous OVA-specific CTLs, the tumor growth was markedly inhibited, which was attributed to the significant antigen presentation on the tumor cells. Overall, the MMP9-responsive conjugates bearing foreign antigens might have the potential as an alternative to CTL-based cancer immunotherapeutics.

Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalJournal of Controlled Release
Volume267
DOIs
Publication statusPublished - 10 Dec 2017
Externally publishedYes

Keywords

  • Antigen delivery
  • Cancer immunotherapy
  • Foreignization
  • Hyaluronic acid
  • Matrix metalloproteinase 9 (MMP9)
  • PEGylation

Cite this

Shin, Jung Min ; Oh, Se Jin ; Kwon, Seunglee ; Deepagan, V. G. ; Lee, Minchang ; Song, Seok Ho ; Lee, Hyo Jung ; Kim, Suyeon ; Song, Kwon Ho ; Kim, Tae Woo ; Park, Jae Hyung. / A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy. In: Journal of Controlled Release. 2017 ; Vol. 267. pp. 181-190.
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abstract = "The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen. The MMP9-cleavable linker was introduced between PEG and the HA backbone to facilitate the detachment of the PEG corona from the conjugate at the tumor site. From the in vitro cellular uptake study, it was revealed that the conjugate was effectively taken up by the CD44-expressing TC-1 cancer cells in the presence of MMP9 via receptor-mediated endocytosis. When the conjugate was systemically administered into the tumor-bearing mice with endogenous OVA-specific CTLs, the tumor growth was markedly inhibited, which was attributed to the significant antigen presentation on the tumor cells. Overall, the MMP9-responsive conjugates bearing foreign antigens might have the potential as an alternative to CTL-based cancer immunotherapeutics.",
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author = "Shin, {Jung Min} and Oh, {Se Jin} and Seunglee Kwon and Deepagan, {V. G.} and Minchang Lee and Song, {Seok Ho} and Lee, {Hyo Jung} and Suyeon Kim and Song, {Kwon Ho} and Kim, {Tae Woo} and Park, {Jae Hyung}",
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Shin, JM, Oh, SJ, Kwon, S, Deepagan, VG, Lee, M, Song, SH, Lee, HJ, Kim, S, Song, KH, Kim, TW & Park, JH 2017, 'A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy', Journal of Controlled Release, vol. 267, pp. 181-190. https://doi.org/10.1016/j.jconrel.2017.08.032

A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy. / Shin, Jung Min; Oh, Se Jin; Kwon, Seunglee; Deepagan, V. G.; Lee, Minchang; Song, Seok Ho; Lee, Hyo Jung; Kim, Suyeon; Song, Kwon Ho; Kim, Tae Woo; Park, Jae Hyung.

In: Journal of Controlled Release, Vol. 267, 10.12.2017, p. 181-190.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy

AU - Shin, Jung Min

AU - Oh, Se Jin

AU - Kwon, Seunglee

AU - Deepagan, V. G.

AU - Lee, Minchang

AU - Song, Seok Ho

AU - Lee, Hyo Jung

AU - Kim, Suyeon

AU - Song, Kwon Ho

AU - Kim, Tae Woo

AU - Park, Jae Hyung

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AB - The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen. The MMP9-cleavable linker was introduced between PEG and the HA backbone to facilitate the detachment of the PEG corona from the conjugate at the tumor site. From the in vitro cellular uptake study, it was revealed that the conjugate was effectively taken up by the CD44-expressing TC-1 cancer cells in the presence of MMP9 via receptor-mediated endocytosis. When the conjugate was systemically administered into the tumor-bearing mice with endogenous OVA-specific CTLs, the tumor growth was markedly inhibited, which was attributed to the significant antigen presentation on the tumor cells. Overall, the MMP9-responsive conjugates bearing foreign antigens might have the potential as an alternative to CTL-based cancer immunotherapeutics.

KW - Antigen delivery

KW - Cancer immunotherapy

KW - Foreignization

KW - Hyaluronic acid

KW - Matrix metalloproteinase 9 (MMP9)

KW - PEGylation

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EP - 190

JO - Journal of Controlled Release

JF - Journal of Controlled Release

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