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Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8(+) T cell-mediated anti-tumor immunity

Authors
Seo, Soo HongHan, Hee DongNoh, Kyung HeeKim, Tae WooSon, Sang Wook
Issue Date
Mar-2009
Publisher
SPRINGER
Keywords
Hydrogel; GMCSF; Cancer drugs; Chemo-immunotherapy
Citation
CLINICAL & EXPERIMENTAL METASTASIS, v.26, no.3, pp.179 - 187
Journal Title
CLINICAL & EXPERIMENTAL METASTASIS
Volume
26
Number
3
Start Page
179
End Page
187
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13815
DOI
10.1007/s10585-008-9228-5
ISSN
0262-0898
Abstract
Cancer treatments consisting of a combination of chemotherapy and immunotherapy have been vigorously exploited to further improve the efficacy of cancer therapies. In this study, we utilized a chitosan hydrogel (CH) system loaded with GMCSF and a cancer drug as a chemo-immunotherapeutic agent in an effort to assess the effects on tumor growth in mice using TC-1 cervical tumor cells, which express the tumor-specific antigen, HPV-16 E7. The growth of TC-1 tumors was significantly reduced in mice treated with a CH harboring a cancer drug (doxorubicin (DOX), cisplatin (CDDP), or cyclophosphamide (CTX)) and GMCSF (CH-a cancer drug + GMCSF), as compared to other groups that were treated with CH containing only a cancer drug(CH-a cancer drug) or GMCSF(CH-GMCSF). Among the cancer drugs, CTX exerted the most potent anti-tumor effects. Interestingly, the intra-tumoral injection of CH-a cancer drug + GMCSF induced a significant E7-specific CD8(+) T cell immune response as compared to CH-GMCSF or CH-a cancer drug. This enhancement of tumor antigen-specific CD8(+) T cell immunity was associated principally with the anti-tumor effects induced by CH-CTX + GMCSF, as demonstrated by antibody depletion. Collectively, the aforementioned results indicate that co-treatment of tumors with a combination of GMCSF and a cancer drug incorporated into a CH system results in synergistic anti-tumor effects, which occur via the induction of a tumor antigen-specific CD8(+) T cell-mediated anti-tumor immunity. This study demonstrates the use of a biodegradable hydrogel system for the co-delivery of an immunoadjuvant and an anti-cancer drug for successful chemo-immunotherapy.
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