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.
