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B7-H3 and 4-1BBL Cooperatively Enhance the Antitumor Response of CD8 T Cells in Oral Cancer

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The aim of this study was to enhance the antitumor immunity of CD8 T cells directed against human oral cancer using B7-H3 and 4-1BBL gene transfer. Recombinant replication-defective adenovirus 5 (Adv) expressing human 4-1BBL, B7-H3 or 4-1BBL/B7-H3 was constructed using the two-plasmid rescue method. Primary human oral cancer cell vaccines (OCV) were prepared by treating cells with 20 μg/ml mitomycin-C after primary human oral cancer cells were infected with Adv transduced with 4-1BBL, B7-H3, 4-1BBL/B7-H3 or control Adv. Then, autologous, purified CD8 T cells were stimulated by coculture with OCV for 4 days. At the end of the culture, CD8 T cell activation was evaluated by ELISA to assay the production of IFNγ and IL-2 in the culture supernatants. Cytotoxic CD8 T cell effector function was analyzed by a 51Chromium (Cr)-release assay, and CD8 T cell proliferation was evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays. Primary human oral cancer cells expressed low levels of B7-H3 and 4-1BBL and weakly stimulated autologous T cells. The primary human oral cancer cell vaccine transduced with the combination of 4-1BBL with B7-H3 retroviruses resulted in significantly enhanced CD8 T cell activation and proliferation. This was associated with increased IFN and IL-2 production by CD8 T cells and improved CD8 T cell proliferation. CD8 T cells stimulated with the autologous B7-3/4-1BBL primary human oral cancer cell vaccine efficiently killed the autologous parental B7-H3/4-1BBL primary human oral cancer cells. Strong CD8 T cell activation, proliferation and longer survival time could be obtained by this vaccine. These data provide a mechanism for developing tumor vaccines using modified tumor cells in patients with oral cancer.
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Keywords: 4-1BBL; B7-H3; CD8 T CELL; PRIMARY ORAL CANCER CELL

Document Type: Research Article

Publication date: February 1, 2011

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  • ADVANCED SCIENCE LETTERS is an international peer-reviewed journal with a very wide-ranging coverage, consolidates research activities in all areas of (1) Physical Sciences, (2) Biological Sciences, (3) Mathematical Sciences, (4) Engineering, (5) Computer and Information Sciences, and (6) Geosciences to publish original short communications, full research papers and timely brief (mini) reviews with authors photo and biography encompassing the basic and applied research and current developments in educational aspects of these scientific areas.
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