EBNK-001: Pioneering Off-the-Shelf NK Cell Therapy for Solid Tumors

EBNK-001 represents a promising advancement in cancer immunotherapy as an “off-the-shelf” allogeneic natural killer (NK) cell product designed for multi-dose administration in patients with advanced solid tumors. Unlike autologous therapies that require individual patient cell harvesting and processing, EBNK-001 leverages healthy donor-derived NK cells, enabling immediate availability without lengthy manufacturing delays. This off-the-shelf approach addresses key limitations of personalized cell therapies, such as high costs, production variability, and restricted access, making NK cell treatment scalable for broader clinical use.
​The core rationale behind EBNK-001 stems from NK cells’ innate ability to recognize and destroy tumor cells without prior sensitization, targeting stress-induced ligands like MICA/B and ULBPs overexpressed on cancer cells while sparing healthy tissue. In solid tumors, where T-cell infiltration often fails due to immunosuppressive microenvironments, NK cells offer advantages through their Fc receptor-mediated antibody-dependent cellular cytotoxicity (ADCC) and cytokine-triggered activation. To optimize efficacy, the therapy incorporates lymphodepleting chemotherapy with cyclophosphamide and fludarabine (CY/FLU), which depletes endogenous lymphocytes, creates a cytokine-rich niche, and promotes engraftment and expansion of infused NK cells.

Supporting this, low-dose interleukin-15 (IL-15) is administered post-infusion to enhance NK cell survival, proliferation, and cytotoxicity by signaling through IL-15 receptors, countering the short lifespan typical of ex vivo-expanded NK cells. Some trial arms combine EBNK-001 with pembrolizumab, a PD-1 inhibitor, to synergistically overcome tumor immune evasion—NK cells directly kill while checkpoint blockade reactivates exhausted T cells. This multi-modal strategy aims to generate durable responses in refractory cancers like sarcoma, renal cell carcinoma, glioblastoma, colorectal, esophageal, and ovarian tumors.

Clinical trial.