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orthoIL-2 3A10 is a mutant interleukin-2 (IL-2) cytokine engineered to have highly specific activity for an orthogonal, mutated IL-2 receptor beta (orthoIL-2Rβ), and not the wild-type IL-2 receptor. This selectivity is achieved by multiple amino acid substitutions that prevent activation of native immune cells by wild-type IL-2 pathways. In preclinical models, orthoIL-2 3A10 can selectively expand engineered T cells that express orthoIL-2Rβ, supporting the safe and targeted enhancement of adoptive cell therapies (ACT) such as chimeric antigen receptor T cells (CAR-T). Compared to other IL-2 mutants, orthoIL-2 3A10 demonstrates superior orthogonality (negligible activity on wild-type T cells), enabling in vivo expansion of transferred therapeutic T cells with minimal off-target immune activation and toxicity. The molecule has been evaluated both as native protein and in a mouse serum albumin-fused form to improve circulating half-life, with both forms retaining selectivity for orthoIL-2Rβ-engineered T cells. Its primary utility is experimental and preclinical, in enhancing the efficacy and safety of T cell-based immunotherapies in cancer models[1][2][4][5].
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