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CD19 t-haNK + rituximab + nogapendekin alfa inbakicept is a **combination immunotherapy regimen** under clinical investigation for the treatment of B-cell lymphomas, particularly in patients with recurrent or refractory disease. This combination integrates three modalities: - **CD19 t-haNK**: An engineered off-the-shelf, allogeneic NK cell therapy expressing a CD19-specific chimeric antigen receptor (CAR) and high-affinity CD16 (FcγRIIIa) receptor. This design enables both direct targeting and lysis of CD19-expressing B-cell malignancies, as well as enhanced antibody-dependent cellular cytotoxicity (ADCC) when combined with therapeutic antibodies[3][8]. It acts through innate NK cytotoxicity, CAR-targeted killing, and antibody-mediated mechanisms. - **Rituximab**: A monoclonal antibody targeting CD20 on B cells, mediating cell death primarily through ADCC, complement-dependent cytotoxicity, and direct apoptosis. - **Nogapendekin alfa inbakicept**: A recombinant fusion protein consisting of interleukin-15 (IL-15) fused to an IL-15 receptor alpha sushi domain, designed to stimulate the proliferation and activation of NK cells and CD8+ T cells, thus providing an immunostimulatory environment. The therapy aims to deliver robust B-cell lymphoma cytotoxicity by combining direct antigen-restricted killing (via CAR-NK and antibody) with immune amplification (via cytokine support)[6][8].
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