simlukafusp alfa

Simlukafusp alfa is a recombinant fusion protein (immunocytokine) that combines a human monoclonal antibody targeting fibroblast activation protein-alpha (FAP) with an engineered variant of interleukin‑2 (IL‑2v). The antibody component binds to FAP, which is highly expressed on cancer-associated fibroblasts in the tumor microenvironment but rarely found in normal tissues. The IL‑2 variant retains affinity for the IL‑2Rβγ receptor complex but has abolished binding to IL‑2Rα, resulting in selective activation of immune effector cells such as CD8+ T cells and natural killer (NK) cells while minimizing stimulation of regulatory T cells. This design aims to enhance antitumor immunity and improve responses when combined with checkpoint inhibitors like PD-(L)1 blockers. Simlukafusp alfa was developed by Roche/Chugai Pharmaceutical for use in various solid tumors, including metastatic pancreatic ductal adenocarcinoma, renal cell carcinoma, malignant melanoma, diffuse large B cell lymphoma, and cervical squamous cell carcinoma. Clinical development was discontinued after phase 1/phase 2 trials due to portfolio prioritization[1][3][4][5][6][7].

Other names

anti-fap/interleukin-2 fusion protein ro6874281