Pavurutamab

Pavurutamab (AMG-701) is a bispecific T cell engager molecule that anti-CD3 and anti-B cell maturation antigens (BCMA). Pavurutamab has an extended half-life based on Pacanalotamab (HY-P99798). The Fc of Pavurutamab is coupled to molecules to improve pharmacokinetic parameters. Pavurutamab has potential applications in immune regulation and multiple myeloma (MM)[1][2][3][4].

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

B cell maturation antigens, BCMA[1]

Pavurutamab (0-10000 pM；48 h) 诱导 CD69+、CD25+ T 细胞活化和 IFNγ、TNFα、IL-2、IL-4、IL-6、IL-10 细胞因子分泌[5]。

Pavurutamab (0.02、0.2 和 2 mg/kg；静脉注射；第 3、8、13 天单剂量) 在小鼠异种移植模型中以时间和剂量依赖的方式减少肿瘤体积[5]。 Pavurutamab (0.005、0.05 和 0.5 mg/kg；静脉注射；每 5 天给药 6 次，持续 30 天) 在移植 L-363 多发性骨髓瘤 (MM) 细胞的 NOD/SCID 小鼠中，以时间和剂量依赖的方式减少肿瘤体积并提高存活率[5]。 Animal Model: Female NOD/SCID mice transplanted with NCI-H929 MM cells mixed with PBMCs[5]. Dosage: 0.02, 0.2 and 2 mg/kg. Administration: Intravenous injection; single dose on days 3, 8, 13. Result: Reduced tumor volume. Animal Model: NOD/SCID mice orthotopically transplanted with L-363 MM cells[5]. Dosage: 0.005, 0.05 and 0.5 mg/kg. Administration: Intravenous injection; every 5 days for 6 administrations, starting from day 9 and lasting for 30 days. Result: Reduced tumor volume and increased survival.

[1]. Sheridan C. Bispecific antibodies poised to deliver wave of cancer therapies. Nat Biotechnol. 2021 Mar;39(3):251-254.  

[2]. Goldsmith SR, et al. Bispecific Antibodies for the Treatment of Multiple Myeloma. Curr Hematol Malig Rep. 2022 Dec;17(6):286-297.  

[3]. Cho SF, et al. The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models. Blood Adv. 2020 Sep 8;4(17):4195-4207.  

[4]. Harrison S J, et al. A phase 1 first in human (FIH) study of AMG 701, an anti-B-cell maturation antigen (BCMA) half-life extended (HLE) BiTE®(bispecific T-cell engager) molecule, in relapsed/refractory (RR) multiple myeloma (MM)[J]. Blood, 2020, 136: 28-29.

[5]. Goldstein RL, et al. AMG 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys. Blood Adv. 2020 Sep 8;4(17):4180-4194.