On July 8, 2020 Cue Biopharma, Inc. (NASDAQ: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the body, reported the peer-reviewed publication of data focused on generation and evaluation of libraries of checkpoint molecules with directed mutations providing novel biological properties in a paper titled "Mechanistic dissection of the PD-L1:B7-1 co-inhibitory immune complex (Press release, Cue Biopharma, JUL 8, 2020, View Source [SID1234608301])."
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In this work, researchers focused primarily on the recently described interaction between B7-1 and PD-L1, two molecules within the B7 superfamily, which are of critical importance for controlling anti-tumor immunity, autoimmunity and infectious diseases. By combining cell microarray and high-throughput FACS methods to screen binding events and map binding interfaces, selective mPD-L1 and mB7-1 mutants with distinct biochemical and functional properties were generated that altered the binding interactions between PD-1 and PD-L1, and CTLA-4 and B7-1 as well as the recently described PD-L1 and B7-1 binding interaction.
"Our efforts expand upon the fundamental understanding of critical binding interactions and related downstream signaling cascades by more completely defining the molecular interactions between these key cell surface molecules," said Steven C. Almo, Ph.D., professor and chair of biochemistry, professor of physiology & biophysics and the Wollowick Family Foundation chair in multiple sclerosis and immunology at Albert Einstein College of Medicine, and co-founder of Cue Biopharma. "Through these studies we are able to decipher specific molecular and atomic insights to engineer and generate molecules with unique biochemical and functional properties with the aim of developing more efficacious treatments with fewer unwanted side effects."
This approach augments and supplements Cue Biopharma’s Immuno-STAT and Neo-STAT platforms, leveraging rational protein engineering to generate therapeutic frameworks possessing desirable drug properties while attenuating and/or abrogating unwanted, deleterious effects. CUE-101, Cue Biopharma’s lead asset from the IL-2 based CUE-100 Series, was rationally engineered to enhance the selective activation of the beneficial CD8+ anti-tumor T cells, while abrogating the effects on other immune cell populations that are deleterious to cancer therapy, such as regulatory T cells. A CUE-101 Phase 1 monotherapy trial is ongoing, with enrollment of patients in dose escalation at 13 leading centers in the United States for the treatment of post first-line metastatic and recurrent HPV+ advanced head and neck cancer. Early data metrics from this trial are encouraging with demonstration of safety and tolerability, dose proportional exposure pharmacokinetics (PK) and early, albeit anecdotal, evidence of biologic activity through pharmacodynamics (PD) biomarkers and clinical benefit.
"We are highly encouraged by these findings and further research being conducted in Dr. Almo’s laboratory, which provides us with additional, novel insights into immune receptors," said Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma. "Learnings from this important work will augment and further advance our internal efforts to build out the Immuno-STAT and Neo-STAT platforms and enhance our ability to dial-in/dial-out specific molecular interactions for the therapeutic modulation of the immune system in cancer, autoimmune diseases and chronic infectious diseases."
Albert Einstein College of Medicine and its faculty members acknowledge the following relationships with Cue Biopharma, Inc.: Dr. Almo holds equity in Cue Biopharma, Inc., receives royalties from existing license agreements between Einstein and Cue, and is a member of its Science Advisory Board; Dr. Garrett-Thomson receives royalties; and Albert Einstein College of Medicine holds equity in Cue and receives royalties.