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01-03-2009 | Research Paper

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: Soo Hong Seo, Hee Dong Han, Kyung Hee Noh, Tae Woo Kim, Sang Wook Son

Published in: Clinical & Experimental Metastasis | Issue 3/2009

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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Title: 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: Soo Hong Seo
Hee Dong Han
Kyung Hee Noh
Tae Woo Kim
Sang Wook Son
Publication date: 01-03-2009
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 3/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-008-9228-5

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