NK cells mediate the anti-tumor effects of E1-deleted, type 5 adenovirus in a human tumor xenograft model

SCH58500 (ACN53) is a recombinant adenovirus expressing human p53 for gene therapy of cancer. In preclinical studies, SCH58500 has shown efficacy agai nst many tumor-types with non-functional p53. This activity arises from bot h p53-mediated and adenovirus vector-mediated mechanisms. The importance of NK cells for adenovirus-mediated tumor suppression after intratumoral dosi ng was demonstrated using MDA-MB-231 human breast cancer xenografts in SCID (defective T and B cell response) and SCID-Beige (defective T, B, and NK c ell response) mice. There was no adenovirus vector-mediated anti-tumor acti vity in SCID-Beige mice. Dexamethasone (Dex) is a potent suppressor of the cellular immune response to recombinant adenovirus in mice and rats. Dex ab olished growth suppression caused by adenovirus vector, but did not interfe re with the anti-tumor efficacy of p53. Supression of NK cell activity in S CID mice using intravenous administration of a neutralizing antibody had th e same effect as Dex. These data support a role for NK cells in adenovirus vector-mediated anti-tumor efficacy.