Indirect mechanisms of action of a novel IgG1 monoclonal antibody, NEO-201, that enhance immune killing of tumor
NEO-201 is an IgG1 mAb targeting variants of CEACAM5/6 that demonstrates tumor sensitivity and specificity. Functional analysis revealed that NEO-201 is capable of engaging innate immune effector mechanism including ADCC and CDC to directly kill tumor cells expressing its target. Previous studies demonstrated safety/tolerability in non-human primates, and an ongoing clinical trial at the NCI is currently exploring its dosing and safety. We have explored indirect mechanisms of its action that may enhance immune tumor killing. NEO-201 can block the interaction between CEACAM5 expressed on tumor cells and CEACAM1 expressed on NK cells to reverse CEACAM1-dependent inhibition of NK cytotoxicity. Phenotypic and functional analyis on human regulatory T cells (Tregs) in vitro also showed that NEO-201 can target and eliminate Tregs, suggesting that this tumor-targeting mAb may also mediate the down regulation of the Treg-mediated immunosuppression of anticancer immunity.
Philip M Arlen, Christina M Annunziata, Massimo Fantini, M. Pia Morelli, and Kwong Y Tsang.