AB821

AB821 is a next-generation, cis-targeted interleukin-21 (IL-21) immunotherapy engineered to selectively activate CD8+ T cells for the treatment of solid tumors. Developed by Asher Bio, AB821 fuses a CD8-targeting antibody with an IL-21 mutein that has attenuated binding to the IL-21 receptor and a reduced positive charge profile. This design confers over 1000-fold selectivity for CD8+ T cells compared to other immune cell types, such as B cells, NK cells, and CD4+ T cells. By focusing activity on CD8+ T cells—the primary drivers of anti-tumor immunity—AB821 aims to maximize efficacy while minimizing toxicity and off-target effects associated with wild-type IL-21. Mechanistically, AB821 promotes cytotoxicity, memory cell differentiation, survival, and reinvigoration of exhausted CD8+ T cells within the tumor microenvironment. Preclinical studies demonstrate that AB821 restores cytotoxic potential in exhausted tumor-infiltrating lymphocytes (TILs), increases granzyme B and perforin expression in human models, and shows potent anti-tumor activity both as monotherapy and in combination with anti-PD-1 therapy in checkpoint inhibitor–refractory mouse models. The drug is being developed primarily for oncology indications where resistance to PD-1 or IL-2 therapies is observed[1][3][5][6][9].

Other names

CD8-targeted IL-21CD-8-targeted IL-21CD 8-targeted IL-21CD8+ T cell selective IL-21cis-targeted IL-21 fusion protein