Lixte Candidate Reported to Convert Immunologically Unresponsive (“Cold”) to Responsive (“Hot”) Tumors

 Outside research shows that in models of colorectal, triple-negative breast and pancreatic cancer, LB-100 induces molecular changes that render the cancers more vulnerable to immunotherapy

 Lixte Biotechnology Holdings, Inc. (Nasdaq: LIXT), a clinical-stage drug discovery company developing pharmacologically active drugs for use in cancer treatment, announced today that in preclinical studies its lead clinical compound, LB-100, a protein phosphatase (PP2A) inhibitor, was found to increase the responsiveness of diverse cancers to immunotherapy. In Nature Communications (15 Dec 2021), lead author Yu-Ting Yen and colleagues at the China Medical University and Hospital, Taichung, Taiwan reported that treatment with LB-100 is associated with new antigen production, tumor infiltration of cytotoxic T cells, and enhanced responsiveness to immune checkpoint blockade in mouse models of colorectal, triple-negative breast, and pancreatic cancer. The authors state that “these data indicate that PP2A inhibition can be used to change the intrinsic and extrinsic factors of tumors to improve the success rate of anti-cancer immunotherapy.”

Lixte’s founder and CEO, John S. Kovach M.D, commented that “recent advances in therapy with immune checkpoint inhibitors have been a true breakthrough in the development of more effective and less toxic treatment for many cancers. Unfortunately, most cancer patients do not respond to immunotherapy. There are widespread efforts to find pharmacologic and/or immunologic ways to turn unresponsive (‘cold’) tumors into responsive (‘hot’) tumors. Cancers with a molecular abnormality termed microsatellite-instability (MSI) stemming from a defect in a DNA repair enzyme are generally ‘hot’ tumors, that is, tumors responsive to immunotherapy. Yen and colleagues now report that pharmacologic inhibition of PP2A by LB-100 modifies two distinct molecular pathways resulting in conversion of microsatellite stable (MSS) tumors into MSI tumors sensitive immune checkpoint blockade therapy.”

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