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.
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) 2023 Annual Meeting –
Poster Title: | Maximizing NK Cell Immunotherapy in Prostate Cancer vis TriKEs |
Abstract: | 1180 |
Date: | |
Time: | |
Presenter: |
*Drs
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