Celldex presents emerging MerTK antibody program
Celldex Therapeutics presented data from the company's MerTK antibody program in a poster session today at the Society for Immunotherapy of Cancer's 33rd Annual Meeting. MerTK's expression in innate immune cells is believed to negatively regulate immune responses and genetic removal of MerTK renders mice resistant to some tumors. As detailed in the presentation, Celldex developed a large panel of antibodies to MerTK and investigated their ability to enhance activation of innate immune cells. Two lead candidate human anti-MerTK antibodies were then selected based on their potent induction of cytokines from human macrophages, dendritic cells, and monocytes. Treatment of dendritic cells with the MerTK antibodies led to production of a broad array of pro-inflammatory cytokines and chemokines. Isolated peripheral blood monocytes were found to express high levels of MerTK and were similarly activated by the MerTK antibodies. Emerging proof of concept data was established in preclinical models. Using a surrogate anti-mouse MerTK antibody, similar increases in the levels of cytokines were observed in the blood of mice shortly after treatment with the antibody. The anti-mouse MerTK antibody led to increased survival when dosed alone or in combination with a PD-1 inhibitor in a colon cancer model. To test the lead clinical candidates, which bind to human and not mouse MerTK, Celldex generated human MerTK transgenic mice that were shown to appropriately express and regulate human MerTK on macrophages. This will now allow testing of the anti-human MerTK mAbs in inflammation and tumor models. Collectively, the data support that anti-MerTK mAbs can modulate MerTK activity consistent with its role as a negative immune regulator and provide an exciting new approach to enhance innate immune function in cancer. Celldex is currently completing the preclinical studies for selection of the lead candidate to advance into development activities. These studies include investigating the antitumor effect of combinations with Celldex's immunotherapy product candidates.