Adenoviral B7-H3 therapy induces tumor specific immune responses and reduces secondary metastasis in a murine model of colon cancer.
Current cancer gene therapies aim at 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. 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. Colon cancers were established by orthotopic injection of syngeneic colon cancer cells into the cecum on Balb/c mice. After two weeks, these mice were treated by intratumoral injection of an adenovirus expressing mouse B7-H3 (Ad-B7-H3-GFP) or a control virus (Ad-GFP). Ad-B7-H3-GFP treatment resulted in a reduction of tumor size compared to the controls. In addition, the occurrence of secondary metastasis 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<or=0.05). Ad-B7-H3-GFP treated animals showed significantly higher frequencies of tumor-specific interferon-gamma producing CD8+ T-cells (p<or=0.05) and higher interleukin-12 levels (p<or=0.01) than control animals. 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.
Lupu
Catalin M
CM
Department of Gastroenterology, University of Heidelberg, Germany.
Eisenbach
Christoph
C
Lupu
Alaviana D
AD
Kuefner
Michael A
MA
Hoyler
Birgit
B
Stremmel
Wolfgang
W
Encke
Jens
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics / Q000494:pharmacology; D002455:Cell Division; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control*
D060887:B7 Antigens; D018122:B7-1 Antigen; C486038:Cd276 protein, mouse