On November 12, 2021 CERo Therapeutics, Inc., a biopharmaceutical company pioneering the development of novel autologous engineered immune cell therapies, reported the results from preclinical in vitro studies describing the characterization of novel chimeric engulfment receptor (CER) T cells (Press release, Cero Therapeutics, NOV 12, 2021, View Source [SID1234595466]). CERs are genetically engineered proteins that bind to tumor-agnostic, inducible stress ligands on the surface of tumor cells to provoke tumor-specific cytotoxicity and innate immune functions such as engulfment and antigen presentation. The data, which are being presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021), demonstrate that T cells engineered to express CERs exhibit multifunctional properties of both innate and adaptive immune responses and suggest the potential for CER T cells to overcome barriers associated with existing adoptive cell-based therapies.
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"These studies highlight for the first time the unique orthogonal profile of CER T cells to combine the tumor cell clearance attributes of macrophages and dendritic cells of the innate immune system with the T-cell activation of the adoptive immune system into a single engineered T cell," said Daniel Corey, MD, founder and CEO of CERo. "One of the limitations of activated T cells is their poor ability to present antigens due to inefficient antigen capture. In contrast, CER T cells facilitate antigen capture, processing and presentation, and impart target-dependent cytokine function, thereby offering a possible means of improving the therapeutic potential of engineered cell therapies."
In the studies, CER T cell constructs containing an extracellular phagocytic receptor were characterized for multiple functions, including cytotoxicity in combination with a Bruton’s tyrosine kinase inhibitor (BTKi), tumor cell fragment uptake, T-cell activation, cytokine induction, and antigen-presenting cell (APC)-like activity. Results of these in vitro studies showed that CER T cells synergized with a BTKi to enhance killing of a mantle cell lymphoma tumor cell line. Further, CER T cells exhibited abilities to capture tumor cell fragments and induce expression of T-cell activation markers and cytokines. CER T cells containing a toll-like receptor (TLR) domain also showed enhanced ability to present exogenous antigen and activate antigen-specific TCR T cells.
The poster entitled "Enhanced antigen capture, antigen-presenting cell (APC)-like function, and cytotoxic responses with chimeric engulfment receptor (CER) T cells" (Abstract #207) is now accessible virtually via the SITC (Free SITC Whitepaper) website and in person today from 7:00 a.m. – 8:30 p.m. ET in Exhibit Hall E.
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.