On July 5, 2023 CoImmune, Inc., a clinical stage immuno-oncology company working to redefine cancer treatment using best-in-class cellular immunotherapies, reported the publication of preclinical data demonstrating that a strategy based on the company’s proprietary Chimeric Antigen Receptor-Cytokine Induced Killer (CAR-CIK) cell platform provides advantages over single-targeting CARs including improved efficacy and high specificity in a model of acute myeloid leukemia (AML) (Press release, CoImmune, JUL 5, 2023, View Source [SID1234633065]). The preclinical data are published in Blood Advances, a peer-reviewed journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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"CAR-engineered T-cells have demonstrated high therapeutic potential, but further development is required to ensure a safe and durable disease remission in AML," said Andrea Biondi, M.D., Professor of Pediatrics at the University of Milano-Bicocca and Scientific Director of the M. Tettamanti Research Center. "The impressive safety profile and encouraging activity of CAR-CIK cells is particularly attractive in the AML setting, in which older age and comorbidities hamper adoptive cell therapy options because of the risk of severe cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome."

The publication, titled, "IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML," describes an approach to developing CAR-CIK cells that co-express a first-generation low affinity anti-CD123 interleukin-3–zetakine (IL-3z) and an anti-CD33 as co-stimulatory receptor without activation signaling domains (CD33.CCR). The dual strategy demonstrated powerful antitumor efficacy against AML targets without any relevant toxicity on hematopoietic stem and progenitor cells (HSPCs) and endothelial cells. Specifically, the researchers found:

CD123 and/or CD33 knockout impairs leukemia growth by modulating multiple cancer pathways in a model of NPM1-mutated AML.
CAR-CIK cells mediate high antileukemic efficacy through transacting co-stimulation.
Low affinity CAR-CIK cells decrease on-target/off tumor toxicity against endothelial and HSPCs in vitro.
Low affinity CAR-CIK cells preserve antileukemic efficacy in vitro and improve antitumor control in vivo.
"CAR T-cell therapy in AML is limited by the absence of an ideal tumor-specific antigen," said Sarah Tettamanti, Ph.D., Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. "In this study, we describe a novel strategy using CAR-CIK cells to target both CD33 and CD123 without the risk of severe on target/off-tumor toxicities. This approach has the potential to improve the outcome of patients with AML."