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Rituximab + T785-ISAC is an immune-stimulating antibody conjugate (ISAC) consisting of the anti-CD20 monoclonal antibody rituximab covalently linked to T785, a small-molecule dual agonist of Toll-like receptor 7 (TLR7) and Toll-like receptor 8 (TLR8). Developed by Bolt Biotherapeutics, this therapeutic candidate is designed to treat B-cell malignancies by combining targeted antibody therapy with localized innate immune activation. The rituximab component targets CD20-expressing tumor cells, while the Fc domain of the antibody facilitates uptake by myeloid-resident Fcγ receptors. Upon internalization, the T785 payload activates TLR7/8 within the endosomes of myeloid cells (such as macrophages and dendritic cells), promoting their maturation, the release of pro-inflammatory cytokines, and the cross-presentation of tumor antigens. This process converts "cold" tumors into "hot" tumors and elicits a durable, T-cell-mediated systemic antitumor immune response.
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