[Oncolytic vaccinia virus expressing CD40L (CD40L-VV) inhibits colorectal cancer cell growth and enhances anti-tumor activity of T cells in tumor-bearing mice].

ABSTRACT

Objective To explore the anti-tumor activity of oncolytic vaccinia virus expressing CD40L (CD40L-VV) against colorectal cancer. Methods The CD40L-VV was obtained by integrating the sequence of CD40L into the skeleton of oncolytic vaccinia virus(VV). The tumor cells were infected with VV and CD40L-VV to verify their oncolytic activity and the expression of CD40L in vitro. After the tumor model of colorectal cancer was treated with VV and CD40L-VV, the tumor growth was monitored, and the phenotype of tumor infiltrating T cells was analyzed by flow cytometry. The anti-tumor activity of recombinant oncolytic VV was also reflected by detecting the production of cytokine and the proliferation activity of tumor infiltrating T cells. Results Microscopic observation and Western blot assay showed that CD40L-VV could effectively infect tumor cells and express CD40L. Cell viability assay showed that VV and CD40L-VV had dose-dependent lytic ability against tumor cells. The results of tumor transplantation in vivo showed that CD40L-VV had stronger ability to inhibiting tumor growth than VV. Flow cytometry showed that tumor infiltrating T cells in the CD40L-VV group had stronger cytokine secretion ability, stronger proliferative activity and more memory cell phenotypes than those in the VV group. Conclusion CD40L-VV can significantly inhibit the growth of colorectal cancer cells and enhance the anti-tumor activity of T cells in vivo.