Simlukafusp alfa (FAP-IL2v) 是一种免疫细胞因子，包括一种抗成纤维细胞活化蛋白 α (FAPα) 的抗体和一种只结合IL-2Rβγ的 IL-2 变体。Simlukafusp alfa 是一种人 IgG1 抗体。
| 生物活性 | Simlukafusp alfa (FAP-IL2v) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAPα) and anIL-2variant that only bindsIL-2Rβγ. Isotype: humanIgG1[1]. |
体外研究
(In Vitro) | 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). |
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体内研究
(In Vivo) | 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(μgoh/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. |
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| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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