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Background HCW11-006 is a multi-functional immune cell stimulator engineered using HCW Biologics’ proprietary TRBC protein scaffold, designed for subcutaneous administration and ex vivo immune cell activation and expansion. This fusion molecule incorporates three common γc cytokines—IL-7, IL-15, and IL-21 - which collectively support T and NK cell proliferation, differentiation, and anti-tumor activity. IL-7 promotes T-cell proliferation and B-cell differentiation, IL-15 enhances CD8+ T cell and NK cell proliferation and function, and IL-21 supports TSCM development, T-cell activation, and NK-cell cytotoxicity. This study evaluates the immunotherapeutic potential of HCW11-006 across several in vivo and ex vivo models.Methods HCW11-006 was evaluated in multiple experimental settings. In vivo studies included a bladder cancer model, an acute myeloid leukemia (AML) NSG mouse model, and an EG7-OVA tumor model. Treatments were administered intravesically or subcutaneously, alone or in combination with standard-of-care therapies such as BCG or immune checkpoint inhibitors (e.g., anti-PD-1). Ex vivo studies assessed the expansion and functionality of CAR-T cells cultured with HCW11-006 compared to standard CD3/CD28 bead stimulation. Re-challenge studies were conducted to assess immune memory response.Results In the bladder cancer model, HCW11-006 combined with BCG increased CD8 + T cell and NK cell infiltration in the bladder. Ex vivo, CAR-T cells expanded with HCW11-006 acquired a TSCM phenotype and demonstrated superior cytotoxicity against cancer cells compared to conventional CAR-T cells. In the AML NSG mouse model, HCW11-006-treated mice exhibited enhanced tumor clearance and long-term anti-tumor responses. In the EG7-OVA tumor model, combination therapy with HCW11-006 and anti-PD-1 significantly reduced tumor growth and prolonged survival, showing synergy over IL-15 + anti-PD-1 combinations. Mice re-challenged with EG7-OVA tumors after initial HCW11-006 + anti-PD-1 treatment resisted tumor growth without additional therapy, indicating a durable memory immune response.Conclusions Across multiple models, HCW11-006 consistently promoted immune cell expansion, enhanced infiltration, and improved anti-tumor activity. The molecule effectively supports the development of T SCM cells, enhances CAR-T cell functionality, and synergizes with immune checkpoint inhibitors. HCW11-006 represents a promising immunotherapeutic agent capable of inducing both immediate and durable anti-tumor immune responses.Ethics Approval HCW Biologics IACUC Committee Protocol number VG2025-009