Simlukafusp alfa

Simlukafusp alfa (FAP-IL2v) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAPα) and an IL-2 variant that only binds IL-2Rβγ. Isotype: human IgG1[1].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

Simlukafusp alfa (FAP-IL2v) 与 huIL-2Rβγ、cyIL-2Rβγ、muIL-2Rβγ、huFAP、cyFAP 和 muFAP的结合常数分别为 43±9 pM、80±20 pM、660±80 pM、0.3 nM、0.23 nM 和 0.5 nM[1]。 Simlukafusp alfa (0-100 nM; 5 days) 在体外激活 CD4+/CD8+ T 细胞和 NK 细胞，但不优先激活 Tregs[1]。 Simlukafusp alfa (0-100 nM) 体外增强 Cetuximab (HY-P9905) 介导的抗体依赖细胞毒性 (ADCC) 和 Cibisatamab (HY-P99011) 介导的 T 细胞依赖细胞毒性 (TDCC)[1]。 Cell Proliferation Assay[1] Cell Line: NK cells, CD4+ and CD8+ T cells Concentration: 0-100 nM Incubation Time: 5 days Result: Induced a dose-dependent proliferation of resting NK cells and resting and activated CD4+ and CD8+ T cells within peripheral blood mononuclear cells (PBMCs).

Simlukafusp alfa (FAP-IL2v) (1 mg/kg; i.v.; weekly for 4 weeks) 在人类癌症小鼠模型中与治疗性抗体联合有效[1]。 Animal Model: huCD16-transgenic SCID mice, lung orthotopic xenograft A549 model[1] Dosage: 1 mg/kg in combination with 25 mg/kg Cetuximab (HY-P9905) as single agents Administration: IV, weekly starting at Day 14 for 4 weeks Result: Achieved greater tumor control than either agent given as monotherapy. Reduced tumor volume and tumor growth. Animal Model: CD-1 mice[1] Dosage: 1, 2 or 4 mg/kg Administration: IV (Pharmacokinetic Analysis) Result: Pharmacokinetic parameters after first dose of human FAP-IL2v (huFAP-IL2v) in CD-1 mice CD-1 mice (n=10 per group) were given 1, 2, and 4 mg/kg huFAP-IL2v by IV administration once weekly. Multiple IV doses at 1 and 2 mg/kg were administered QW for up to a maximum of three doses, at which point toxicity was observed. Only a single dose was administered to the 4-mg/kg IV treatment group because of toxicity in these treatment groups. Blood was sampled at 0.5, 6, 24, 48, 72, and 168 h. huFAP-IL2v dose (mg/kg) Cmax (μg/mL) AUC0-168h (μg•h/mL per mg/kg) CL (mL/d/kg) 1 19.0 557 40.0 2 36.3 479 46.8 4 78.7 541 38.7 AUC0-168h, area under the concentration-time curve from 0 to 168 hours; Cmax, maximum serum concentration observed; CL, total clearance; FAP-IL2v, fibroblast activation protein-α -targeted interleukin 2 variant (IL2v) immunocytokine; hu, humanized; IV, intravenous.

[1]. Waldhauer I, et al. Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy. MAbs. 2021 Jan-Dec;13(1):1913791.