GTB-5550: a New Tri-Specific Natural Killer Cell Engager Moving To Clinical Trials

GTB-5550, a novel tri-specific natural killer (NK) cell engager drug designed to target the B7-H3 antigen has shown notable promise in advancing cancer immunotherapy for solid tumors, particularly prostate cancer and head and neck squamous cell carcinoma (HNSCC). This drug functions by simultaneously binding to CD16 on NK cells, engaging B7-H3 expressed on tumor cells, and delivering an interleukin-15 (IL-15) signal that promotes NK cell survival and activation. The tri-specific design aims to enhance NK cell proliferation and cytotoxic function precisely against B7-H3-positive tumors, an antigen commonly overexpressed in a variety of aggressive solid tumors including advanced prostate cancer.

Preclinical models demonstrated the drug’s strong ability to induce NK cell degranulation, cytokine production, and effective killing of tumor cells under challenging conditions, such as hypoxia and immune suppression caused by myeloid-derived suppressor cells (MDSCs). These data are significant, given that NK cell dysfunction often limits the immune response in the tumor microenvironment of solid cancers like prostate cancer. Additionally, its efficacy in both two-dimensional tumor cell lines and more physiologically relevant three-dimensional spheroid models indicates a robust capacity to function in the complex and immunosuppressive niches found in human tumors.

The tri-specific engager offers a new therapeutic approach for B7-H3-positive tumors ,where resistance to existing treatments remains a major clinical challenge. In prostate cancer models, it has shown potential to overcome suppressive microenvironments and to induce NK cell cytotoxicity even in cases resistant to androgen receptor pathway inhibitors. These encouraging preclinical results support its potential to fill an unmet need for durable and selective immunotherapies in solid tumors.

Currently in late preclinical development and moving towards clinical evaluation with the first patient enrollment forecasted by April 2026, the drug represents a novel class of NK cell engagers that build upon earlier-generation constructs by integrating a cytokine signal to enhance innate immune cell function while maintaining tumor-target specificity. This strategic targeting is intended to minimize systemic toxicities seen with other immunotherapies by restricting potent activation to the tumor vicinity.

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