Adenoviral B7-H3 therapy induces tumor specific immune responses and reduces secondary metastasis in a murine model of colon cancer

Introduction: Current cancer gene therapies aim for the induction of systemic antitumor immune responses. Tumors may deliver antigens to T cells, but may lack the costimulatory signals necessary for mounting an effective response.

Aims: The purpose of this study was to evaluate the efficacy of an adenoviral delivery of the B7-H3 costimulatory molecule in mice to induce antitumor immune responses.

Methods: Colon cancers were established by orthotopic injection of syngeneic colon cancer cells into the cecum on Balb/c mice. After two weeks theses mice were treated by intratumoral injection of an adenovirus expressing mouse B7-H3 (Ad-B7-H3-GFP) or a control virus (Ad-GFP).

Results: Ad-B7-H3-GFP treatment resulted in a reduction of tumor size compared to the controls. In addition, secondary metastasis occurrence was significantly reduced in B7-H3 treated mice compared to control animals (lymph node 7/10 vs. 10/10; liver 2/10 vs. 8/10, p ≤0,05). Ad-B7-H3-GFP treated animals showed significantly higher frequencies of tumor specific Interferon-γ producing CD8+ T-cells (p ≤0,05) and higher Interleukin-12 levels (p ≤0,01) than control animals.

Conclusion: This study demonstrates that adenoviral B7-H3 transfer is able to induce a specific cellular antitumor immune response leading to primary tumor regression and reduction of secondary metastasis in vivo.