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- Title
Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector.
- Authors
Okada, N.; Sasaki, A.; Niwa, M.; Okada, Y.; Hatanaka, Y.; Tani, Y.; Mizuguchi, H.; Nakagawa, S.; Fujita, T.; Yamamoto, A.
- Abstract
Our goal in the present study was to evaluate antitumor effects and frequency of tumor-infiltrating immune cells upon intratumoral injection of RGD fiber-mutant adenoviral vector (AdRGD) encoding the chemokines CCL17, CCL19, CCL20, CCL21, CCL22, CCL27, XCL1, and CX3CL1. Among eight kinds of chemokine-expressing AdRGDs, AdRGD-CCL19 injection most efficiently induced infiltration of T cells into established B16BL6 tumor parenchyma, whereas most of these T cells were perforin-negative in immunohistochemical analysis. Additionally, the growth of AdRGD-CCL19-injected tumors decreased only slightly as well as that of other tumors treated with each chemokine-expressing AdRGD, which indicated that accumulation of naive T cells in tumor tissue does not effectively damage the tumor cells. Tumor-bearing mice, in which B16BL6-specific T cells were elicited by dendritic cell-based immunization, demonstrated that intratumoral injection of AdRGD-CCL17, -CCL22, or -CCL27 could considerably suppress tumor growth and attract activated T cells. On the other hand, AdRGD-CCL19-injection in the immunized mice showed slight increase of tumor-infiltrating T cells compared to treatment using control vector. Collectively, although AdRGD-mediated chemokine gene transduction into established tumors would be very useful for augmentation of tumor-infiltrating immune cells, a combinational treatment that can systemically induce tumor-specific effector T cells is necessary for satisfactory antitumor efficacy.Cancer Gene Therapy (2006) 13, 393–405. doi:10.1038/sj.cgt.7700903; published online 14 October 2005
- Subjects
CANCER treatment; GENE therapy; ANTINEOPLASTIC agents; T cells; CHEMOKINES; MELANOMA; CANCER cells; DRUG resistance in cancer cells
- Publication
Cancer Gene Therapy, 2006, Vol 13, Issue 4, p393
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700903