Antibody technology provides an exciting new approach to enhance innate immune function in cancer
“MerTK has been described as an immune checkpoint in macrophages, dendritic cells and other immune cells,” said
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.
About
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline includes immunotherapies and other targeted biologics derived from a broad set of complementary technologies which have the ability to engage the human immune system and/or directly inhibit tumors to treat specific types of cancer or other diseases. Visit www.celldex.com.
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Source: Celldex Therapeutics, Inc.