On June 27, 2023 CoImmune, Inc., a clinical stage immuno-oncology company working to redefine cancer treatment using best-in-class cellular immunotherapies, reported that it has exercised its option to obtain an exclusive license in the Delta-like Ligand 3 (DLL3)-targeted, allogeneic Chimeric Antigen Receptor-Cytokine Induced Killer (CAR-CIK) cell therapy field to interleukin-18 (IL-18) Armored CAR technology under a prior agreement with Memorial Sloan Kettering Cancer Center (MSK) (Press release, CoImmune, JUN 27, 2023, View Source [SID1234632941]). The company is coupling the technology with allogeneic CIK cells and launched a development program focused on solid tumors with initial trials planned in small cell lung cancer (SCLC).

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"Traditional CAR T cells have proven to be poorly effective against solid tumors due, in part, to the immunosuppressive tumor microenvironment, but we have demonstrated the potential for CAR-CIK cells to be effective in combination with additional technologies that may be able to improve proliferation, persistence and reverse immunosuppression," said Charles Nicolette, Ph.D., Chief Executive Officer of CoImmune. "IL-18 expression has the potential to greatly enhance the potency of DLL3-targeted therapy and we look forward to advancing our development of CMN-009, an IL-18 armored anti-DLL3 CAR-CIK therapeutic for SCLC."

CoImmune has the option to select up to three targets for IL-18 CAR products in the allogeneic cell therapy field under the agreement with MSK. In March 2023, the company announced it had selected CD19 as the first target to support the clinical development of CMN-008 (Armored CAR-CIK cells) in B-cell malignancies. CoImmune plans to file an Investigational New Drug (IND) application for CMN-008 to treat acute lymphoblastic leukemia (ALL) this year.

The DLL3 target has been identified as a tumor-specific cell surface marker on neuroendocrine cancers including SCLC. A paper recently published in Journal of Clinical Investigation, titled, "IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models," describes an effort by researchers including Renier J. Brentjens, M.D., Ph.D., Deputy Director and Chair of Medicine, Roswell Park Comprehensive Cancer Center, to develop a CAR against DLL3 that displays antitumor efficacy in xenograft and murine SCLC models. The data reported show IL-18 armored CAR-DLL3 T cells could eradicate disease at very low doses, especially when combined with a PD-1 checkpoint inhibitor.

"Our preclinical studies with a model of metastatic SCLC demonstrated that IL-18 production increased the activation of both CAR T cells and endogenous tumor-infiltrating lymphocytes," said Dr. Brentjens, who previously developed the IL-18 Armored CAR technology at MSK. "We also observed increased infiltration, repolarization and activation of antigen-presenting cells. Human IL-18-secreting anti-DLL3 CAR T cells were able to eradicate disease at dose levels where standard anti-DLL3 CAR-T cells were ineffective. We saw strong synergy with PD1 checkpoint inhibition, suggesting a potential for curative responses at lower, subtherapeutic administrations of IL-18 armored anti-DLL3 CAR T cells. These results define DLL3-targeting CAR T cells that produce IL-18 as a promising novel strategy against DLL3-expressing solid-tumor cancers."

CoImmune’s IL-18 armored CARCIK-DLL3 product prototype, CMN-009, will be studied in animal models throughout the remainder of 2023. Additional technologies licensed from MSK (e.g., SEAKER, SHIELD) will be tested in combination with CMN-009 to further enhance functionality. The Company expects to initiate IND-enabling studies in the first half of 2024.