Comparison of the anti-tumor activity of native, secreted, and membrane-bound LIGHT in mouse tumor models

The TNF superfamily member LIGHT has potent anti-tumor activity through direct cytotoxicity and activation of the immune response, and is a promising candidate for cancer therapy Natively. LIGHT exists as both a membrane-anchored form and a proteolytically processed, secreted form However, the strength of the antitumor activity of each form of LIGHT has not been well defined Here, to identify the optimal form of LIGHT for cancer gene therapy. we constructed fiber-mutant adenovirus vectors (AdRGD) encoding native full-length LIGHT (LIGHT/FL), stably membrane-anchored LIGHT (LIGHT/mem), and fully secreted LIGHT (LIGHT/sec) We then compared the anti-tumor effects of the different forms of LIGHT in mice by intratumoral injection of each AdRGD We demonstrated that intratumoral injection of AdRGD-LIGHT/sec provided greater tumor suppression than AdRGD-LIGHT/FL, although this effect did not reach statistical significance By comparison, AdRGD-LIGHT/mem had negligible anti-tumor activity We also demonstrated that more CD4+ and CD8+ T cells accumulated inside tumors treated in vivo with AdRGD-LIGHT/sec than in tumors treated with AdRGD-LIGHT/FL or AdRGD-LIGHT/mem These results Suggest that the secreted form of LIGHT might be the optimal form for cancer gene therapy (C) 2009 Elsevier B.V All rights reserved