On May 2, 2022 CERo Therapeutics, Inc., a biopharmaceutical company pioneering the development of novel autologous engineered immune cell therapies, reported new preclinical data to be presented at the 25th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) demonstrating significant anti-tumor effects of chimeric engulfment receptor (CER) T cells when combined with small molecule therapies in both hematologic and solid tumor models (Press release, Cero Therapeutics, MAY 2, 2022, View Source [SID1234613332]).
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CER T cells are multifunctional, genetically engineered T cells that elicit dual cytotoxic and myeloid-like anti-tumor function. CER T-cells, which target a phagocytic ligand that can be induced by small molecules, offer the potential for broad anti-tumor synergisms through a differentiated mechanism of tumor clearance. The data indicate the potential for the unique CER T-cell reprogramming technology to restore immune dysfunction in advanced tumor microenvironments when used in combination with small molecule inhibitors. The differentiated and combined approach offers the potential for more complete and durable responses than targeted agents alone.
"Our technology platform reprograms cytotoxic T cells to build in innate immune functions, creating multifunctional CER T cell products that intersect conventional T-cell and myeloid cell-like functions to attack tumors," said Daniel Corey, MD, founder and Chief Scientific Officer of CERo. "These data show that CER T cells synergize with current standard-of-care targeted therapies and result in improved tumor clearance and immune activation than either therapy alone in lymphoma and ovarian cancer models. We now have evidence in clinically relevant disease models supporting our approach and look forward to advancing our lead candidate toward IND-enabling studies."
In the ovarian cancer model, CER T cells synergized with sub-clinical doses of the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and niraparib to eliminate tumor cells in vitro. In these studies, the addition of PARP inhibitors drove CER T-cell cytokine and proliferation responses against ovarian cancer cell targets compared to untreated samples. By comparison, CER T cells or PARP inhibitors alone demonstrated minimal anti-tumor function. Synergisms were also observed in mantle cell lymphoma (MCL) models with the Bruton’s tyrosine kinase inhibitor ibrutinib. The combinatorial approach cleared 90% of tumor cells at sub-therapeutic concentrations of ibrutinib. CER T cells also proliferated and produced T-cell activation cytokines upon target engagement.
Notably, CER T cells exhibited a differentiated mechanism of tumor clearance via enhanced endo/phagocytosis. In co-cultures with MCL tumor cells, CER T cells showed a 15-fold increase in engulfment activity compared to unmodified T cells. Further, in a model system, CER T cells demonstrated the ability to capture, process, and present tumor antigen, and trigger antigen-specific T-cell responses. Finally, in vivo MCL xenograft studies showed that CERs reduced tumor volume relative to controls, with no overt morbidity.
An oral presentation of the abstract entitled "Tim-4-Chimeric Engulfment Receptor (CER) T Cell Therapy Elicits Phosphatidylserine-Dependent Cytotoxic and Antigen-Presenting Cell-Like Function and Synergizes with Approved BTK Inhibitors for the Treatment of Hematologic Malignancies" (abstract 89) will take place on Monday, May 16, 2022 at 4:45-5:00 p.m. ET during the "CAR T-cells and Beyond" session in Room 102 A/B.
Data from the poster entitled "Tim-4-Chimeric Engulfment Receptor (CER) T Cells Elicit Phosphatidylserine-Dependent Cytotoxic and Innate-Like Function and Synergize with Approved PARP Inhibitors in an Ovarian Cancer Model" (abstract 314) will be presented on Monday, May 16.
About CERo’s Platform Technology
CERo’s technology aims to expand the therapeutic potential of engineered T cell-based therapies by introducing distinct and complementary tumor cell clearance pathways into a single T cell. By engineering T cells to express CERs, CERo’s platform technology enables T cells to target tumors, induce cellular damage, engulf tumor fragments, and clear tumors, effectively harnessing the anti-tumor attributes of both innate and adaptive immune responses. CER T-cell products are designed to generate a more complete and durable anti-tumor response. This novel biology amends itself to combinations with classic CAR T-cell or small molecule therapy and has potential applications in hematologic malignancies and solid tumors.