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

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

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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.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalClinical and Experimental Metastasis
Volume26
Issue number3
DOIs
Publication statusPublished - 2009 Mar 1

Fingerprint

Hydrogel
Chitosan
Immunity
T-Lymphocytes
Pharmaceutical Preparations
Neoplasms
Neoplasm Antigens
Immunotherapy
Immunologic Adjuvants
Human papillomavirus 16

Keywords

  • Cancer drugs
  • Chemo-immunotherapy
  • GMCSF
  • Hydrogel

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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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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AU - Noh, Kyung Hee

AU - Kim, Tae Woo

AU - Son, Sang Wook

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