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
Journal of controlled release : official journal of the Controlled Release Society
2017Aug ; 12 ( 9 ) :.
PMID : 28844759
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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 -
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. CI - Copyright ??2017. Published by Elsevier B.V.
Antigen delivery; Cancer immunotherapy; Foreignization; Hyaluronic acid; Matrix metalloproteinase 9 (MMP9); PEGylation
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