On September 15, 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 preclinical data focused on the in vivo detection of tumor antigen-specific T cells in a paper published in Nature Methods titled, "In vivo detection of antigen-specific CD8 T cells by immuno-positron emission tomography (Press release, Cue Biopharma, SEP 15, 2020, View Source [SID1234608295])." The study was co-authored by Steven C. Almo, Ph.D., co-founder of Cue Biopharma, 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 Hidde Ploegh, Ph.D., a renowned expert in molecular immunology and a member of the program in cellular and molecular medicine at Boston Children’s Hospital.
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In this work, researchers employed dimeric protein scaffolds to develop a novel immuno-positron emission tomography (immunoPET) imaging approach. These protein scaffolds, known as synTacs, consist of Fc-based covalent peptide-major histocompatibility complex (pMHC) dimers, which form the core structure of Cue Biopharma’s Immuno-STAT (Selective Targeting and Alteration of T cells) platform. By targeting synTacs labelled with positron emitting isotopes against specified tumor antigens, researchers were able to specifically and non-invasively detect tumor antigen-specific T cells in murine solid tumor models. In the same study, similar application of synTacs deploying viral antigens could detect and engage virus-specific T cells in the lung tissue.
"These studies demonstrate the remarkable breadth of applications supported by the Immuno-STAT platform, as it enables clinical applications for highly selective targeted treatments of cancer, autoimmune diseases and infectious diseases, but, also as demonstrated in the Nature Methods paper, the potential to serve as prognostics and diagnostics for mechanism-of-action and treatment efficacy by revealing the in vivo distribution of the biologic and its target T cells in diseased tissue," said Dr. Almo.
"This work highlights the power of the Sortase A coupling technology developed in our lab, as it readily allowed the site-specific, stoichiometric and highly reproducible installation of PET imaging tags (64Cu2+ and 89Zr4+ and 18F) for the in vivo tracking of antigen-specific T cells targeting tumor cells and virally infected cells in the disease tissue. These advances highlight the strength of modular biologic platforms, like the Immuno-STAT platform, that can be deployed for targeting and tracking antigen-specific effector lymphocytes in the patients to gain predictive insights into pharmacodynamic and clinical responses," elaborated Dr. Ploegh.
Specific detection of intratumoral T cells by this newly developed immunoPET approach provides further support that the core component of the Immuno-STAT scaffold can penetrate into the tumors and directly engage tumor-resident T cells. These data highlight the modular nature and the broad applicability of the Immuno-STAT platform to selectively deliver cargoes, such as imaging agents or immunomodulatory signals to tumor-resident T cells.
Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma, commented, "We are highly encouraged by these results, as they highlight the inherent advantages of our engineered biologics platforms. Data showing the efficient penetration of the HPV16 E7 targeted synTac into solid tumors are particularly noteworthy, as similar technologies are unable to deliver cargoes past the tumor periphery. Further, this synTac is analogous to our lead asset, CUE-101, which carries a covalently linked IL-2 variant and is currently being evaluated in a Phase 1 trial in HPV16 driven head and neck squamous cell carcinoma."
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. Albert Einstein College of Medicine holds equity in Cue and receives royalties from existing licensing agreements.