On March 23, 2022 Chimeric Therapeutics (ASX:CHM, "Chimeric"), a clinical-stage cell therapy company and an Australian leader in cell therapy, reported that the discovery and preclinical characterization of a CAR T targeting CDH17, currently under development by Chimeric as CHM 2101 has been published as the cover story for the highly prestigious journal Nature Cancer (Press release, Chimeric Therapeutics, MAR 23, 2022, View Source [SID1234610740]).
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Key findings highlighted in the Nature Cancer publication included:
• Strong preclinical safety and efficacy: the CDH17 CAR T completely eradicated tumours, with no relapse or toxicity, in 8 different in vivo models including colorectal cancer (CRC), gastric cancer, pancreatic cancer, and neuroendocrine tumours (NETs).
• Optimal CAR T construct design: the CDH17 CAR T as a third-generation CAR T cell construct was shown to be superior to the 2nd-generation CAR T cell construct, demonstrating complete elimination of solid tumours in vivo. Construct optimization with a very short linker domain further enhanced tumour cell killing.
• Tumour-specific activity: CDH17 CAR T cells infiltrated and destroyed CDH17+ tumours, but not normal CDH17-expressing tissues such as small and large intestines, creating a therapeutic window for CAR T treatment of solid tumours.
The authors conclude that their "findings indicate that CDH17 is an ideal target of CART therapy for GICs (Gastrointestinal Cancers) and NETs (Neuroendocrine Tumours)" and that their studies "suggest that CDH17 is a safe and efficacious target for developing CART therapy to treat GICs and NETs, without toxicity to healthy tissues, motivating further clinical investigation."1
The Nature Portfolio publishes a range of academic journals, magazines and online databases covering science and medicine, and is known to publish some of the world’s most highly prestigious scientific journals. The Nature Cancer journal ‘aims to publish the most significant advances across the full spectrum of cancer research in the life, physical, applied and social sciences, spanning basic preclinical, translational and clinical work’. In July 2021, Chimeric acquired the exclusive rights to develop and commercialize CDH17 (CHM 2101), and in February 2022 announced its commitment to a three-year sponsored research program with the inventors to further the development and understanding of CHM 2101.
"The data published in Nature Cancer are rigorous, scientifically elegant, and suggest great promise for CHM 2101 as a potential CAR T-cell therapy for solid tumours," said Eliot Bourk, Ph.D., Chimeric’s Chief Business Officer and Head of External Innovation. "The optimized construct targeting CDH17 presents a novel and highly differentiated approach to overcoming the challenges observed to date with T-cell therapies in solid tumours."
"We are now rapidly advancing CHM 2101 toward first-in-human clinical studies, with the hope of bringing the promise of cell therapy to life for patients with currently incurable GI cancers," said Chimeric CEO and Managing Director, Jennifer Chow. 1. Feng et al. Nature Cancer, 2022. View Source Authorised on behalf of the Chimeric Therapeutics board of directors by Chairman Paul Hopper