Phase 1 Trial GTB-5550, a Immunotherapy Targeting B7-H3 in Solid Tumors (Including mCRPC)

A new immunotherapy called GTB-5550 targeting B7-H3 on cancer cells has received FDA clearance for its first human trial(expected to start in the first half of 2026), offering fresh hope particularly for advanced prostate cancer patients exhausted by standard treatments. GTB-5550 is a TriKE molecule that binds natural killer (NK) cells from the immune system via their CD16 receptor, boosts them with wild-type IL-15 to multiply and persist, and guides them to B7-H3-overexpressing tumors for precise attack. Think of NK cells as innate killer squads that spot and destroy invaders without prior alerts; tumors evade them through low oxygen, suppressor cells, or hiding proteins, but GTB-5550 serves as a molecular GPS and energizer, linking NK cells to targets, activating their perforin/granzyme weapons, and sustaining the assault even in harsh conditions.

B7-H3 appears on nearly all prostate tumors, spiking in metastatic castration-resistant cases resistant to enzalutamide or abiraterone. Lab tests with prostate cell lines (including enzalutamide-resistant ones) demonstrated GTB-5550 ramps up NK degranulation (releasing kill signals) 3-5 times over controls, boosts interferon-gamma (activation marker) production, and achieves 50-80% cytotoxicity in 2D/3D assays. Critically, under hypoxia mimicking prostate tumor cores or with MDSCs (tumor-protecting myeloid cells), GTB-5550 preserved NK killing at levels 2-4x higher than NK+IL-15 alone, using both healthy and patient-derived NK cells. In xenograft mice with human prostate tumors, treatment halted growth or induced regression, far surpassing untreated or single-component arms, as presented at SITC 2023. These results directly informed the IND, highlighting GTB-5550’s edge in prostate’s immunosuppressive niche.

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