Ll. Nielsen, NK cells mediate the anti-tumor effects of E1-deleted, type 5 adenovirus in a human tumor xenograft model, ONCOL REP, 7(1), 2000, pp. 151-155
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.