Elucidating the mechanisms behind biologics

Cue Biopharma enters into research collaboration with Dr. Michael Dustin and University of Oxford to study Immuno-STAT biologics on T cell immunological synapse formation 

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CAMBRIDGE, Mass.—Cue Biopharma, Inc. has entered into a new research collaboration agreement with Dr. Michael Dustin and the University of Oxford’s Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences. The object of the collaboration is to determine the molecular mechanisms underlying the activity of Cue Biopharma’s IL-2 based CUE-100 series Immuno-STAT (Selective Targeting and Alteration of T cells) biologics.
“Cue Biopharma is pleased to enter into this strategic collaboration with Dr. Dustin and the University of Oxford,” said Saso Cemerski, senior director of immuno-oncology discovery and translational immunology at Cue Biopharma. “Dr. Dustin, the scientific pioneer and founder of the T cell immune synapse field, has made seminal observations contributing [to] our understanding of the biophysical interactions and signaling pathways that underscore immune cell activation, including the mechanistic underpinnings of T cell recognition of antigens. Our strategic collaboration will exploit the state-of-the art technologies pioneered by Dr. Dustin’s lab to elucidate the immune synapse interactions of our IL-2-based CUE-100 series that ultimately result in selective and specific activation of tumor-antigen-specific T cells.”
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This biologic is believed to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been attenuated to achieve preferential selective activation of tumor-specific effector T cells, while reducing the potential for effects on regulatory T cells or broad systemic activation. This could potentially mitigate the dose-limiting toxicities associated with current IL-2-based therapies. 
“We look forward to working with Cue Biopharma on this innovative and promising new technology. We have long appreciated the effects of IL-2 on the immunological synapse, and this research collaboration will allow us to systematically study effects of natural IL-2 and the engineered Immuno-STAT to define potential features of the Immuno-STAT platform that may be driving the selective and preferential modulation of T cells,” added Dustin, who is professor of immunology, Wellcome Trust Principal Research Fellow and director of research at the Kennedy Institute.
Cue Biopharma states that Immuno-STAT biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of the biologic drugs is designed using the company’s proprietary scaffold, and is comprised of a pMHC to provide selectivity through interaction with the T cell receptor and a unique co-stimulatory signaling molecule to modulate the activity of the target T cells.
The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells to T cells during a natural immune response. This design reportedly enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in highly targeted T cell modulation. The drugs are delivered directly in the patient’s body — this differs from other T cell therapeutic approaches, which require the patients’ T cells to be extracted, modified outside the body and then re-infused.
“We anticipate that the findings from this strategic research collaboration will provide important insights into the mechanism of action (MOA) of our IL-2-based CUE-100 series Immuno-STATs.  Understanding the MOA will in turn enhance our ability to detect and interpret pharmacodynamic effects induced in patients treated with our lead immuno-oncology asset, CUE-101, currently being tested in patients with head and neck cancer,” explained Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma. “Learnings from this important work will further advance our internal efforts to build out the Immuno-STAT platform to develop new and effective therapeutics for patients suffering from solid and hematological cancers.”

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