(Anaveon) ANV600は、強力なシスシグナル伝達型IL-2Rβ/γ標的IL-2であり、腫瘍内における幹細胞様CD8 T細胞を効率的に増殖させる。

背景

ANV600 is a novel PD-1 targeted, IL-2Rβ/γ directed IL-2

ANV600 consists of a proprietary PD-1 binding moiety and an IL-2Rβ/γ directed interleukin-2/anti-IL-2 fusion protein, thus targeting the cytokine to PD-1 expressing T cells. The IL-2 agonist arm of ANV600 includes an anti-IL-2 antibody with high affinity to the IL-2Rα binding domain of IL-2. The cytokine is directly fused to the light chain of the antibody through a peptide linker, allowing ANV600 to present IL-2 to the dimeric β/γ IL-2 receptor on CD8 PD-1⁺ T cells, while sterically excluding binding to the high affinity trimeric α/β/γ IL-2 receptor.

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In the tumor microenvironment, the pool of PD-1⁺ T cells is primarily composed of tumor antigen experienced cells. ANV600 potently and selectively proliferates tumor specific PD-1⁺ stem-like CD8 T cells and effector cells, and markedly reduces tumor growth in poorly immunogenic syngeneic mouse tumor models.