On November 6, 2023 GT Biopharma, Inc. (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager, TriKE platform, reported positive preclinical data in highlighting GTB-5550’s potential in prostate cancer (Press release, GT Biopharma, NOV 6, 2023, View Source [SID1234637025]). Martin Felices, PhD, Associate Professor of Medicine at the University of Minnesota, presented these data on Saturday, November 4th at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2023, which is being held in San Diego, California November 1-5.
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Natural killer (NK) cells are being increasingly explored in clinical trials due to their safety profile and ability to mediate tumor killing without prior priming. However, lack of antigen-specific targeting, decreased numbers, and suppressive signals from the tumor microenvironment (TME) of Prostate Cancer (PCa), can negatively impact NK cell efficacy. GTB-5550 was specifically designed as a novel tri-specific killer engager (TriKE) molecule with three components: an arm that engages with CD16, an activating receptor of NK cells, an arm that binds to tumor antigens expressed in prostate cancer (PSMA or B7H3), and an interleukin (IL)-15 moiety that is essential for NK cell survival, proliferation, priming and motility.
"These preclinical findings provide additional support for our TriKE technology and the specific mechanism of action for this construct in promoting NK-specific proliferation, effective killing of target cells and ability to bypass the myeloid-derived suppressor cells (MDSC)-induced suppression of NK cells," stated Dr. Jeffrey Miller*, MD, GT Biopharma’s Consulting Chief Medical Officer and Consulting Chief Scientific Officer. "All of this bodes well as we progress this specific TriKE towards the clinic with the goal of an eventual indication in prostate cancer."
Key findings demonstrated that normal donor and prostate cancer patient NK cells displayed better, specific, degranulation against prostate cancer cell lines in the presence of PSMA or B7H3 TriKEs. NK cell cytotoxicity was also improved, even in the presence of enzalutamide resistant lines, hypoxia, or MDSCs. The TriKE molecules displayed improved tumor control, compared to IL-15 control or no treatment, in xenogeneic models of prostate cancer.
Society For Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2023 Annual Meeting – November 1-5, 2023
Poster Title: Maximizing NK Cell Immunotherapy in Prostate Cancer vis TriKEs
Abstract: 1180
Date: Saturday, November 4, 2023
Time: 2:55 pm -4:25 pm & 10:00 pm – 11:30 pm ET
Presenter: Martin Felices*, PhD, Associate Professor of Medicine, University of Minnesota
*Drs Jeff Miller (consultant CMO) and Martin Felices are consultants for GT Biopharma and hold equity.