Cinrebafusp alfa

Cinrebafusp alfa (PRS 343) is a high affinity CD137/HEr2 bispecfic anticalin-based drug. Cinrebafusp alfa binds to recombinant human HER2 (Kd=0.3 nM) and human monomeric CD137 (4-1BB; Kd=5 nM). Cinrebafusp alfa facilitates T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation, further enhancing T-cell receptor-mediated activity and leading to tumor destruction. Cinrebafusp alfa has the potential for HER2+ solid tumors research[1][2].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

4-1BB:5 nM (Kd)

HER2:0.3 nM (Kd)

Cinrebafusp alfa (PRS 343) 结合表达 HER2 的 MCF-7 细胞和转染人 4-1BB 的 CHO 细胞，在 FACS 测定中 EC50 分别为 7.4 nmol/L，6.2 nmol/L[1 ]。

Cinrebafusp alfa (PRS 343; 0.2-10 mg/kg; 静脉注射; 每周一次; 持续 20 天) 在移植有 HER2 阳性 SK-OV-3 肿瘤细胞的人源化小鼠模型中导致肿瘤生长抑制并且肿瘤浸润淋巴细胞呈剂量依赖性增加[1]。 Cinrebafusp alfa (10 mg/kg; IV; 单剂量) 在雄性 CD-1 小鼠中的终末消除半衰期为 >14 天。Cinrebafusp alfa (3 mg/kg; 静脉注射; 单剂量) 在雄性食蟹猴中的终末消除半衰期约为 4 天[1]。 Animal Model: SK-OV-3 ovarian cancer model in human PBMC-reconstituted NOG female mice, ages 5-7 weeks[1] Dosage: 0.2, 1, 5, 10 mg/kg Administration: IV; once weekly; for 20 day Result: Displayed dose-dependent antitumor efficacy with doses ranging from 4 μg to 100 μg (approximately 0.2 mg/kg to 5 mg/kg), while the 200-μg dose (approximately 10 mg/kg) did not further enhance tumor regression. Led to a significant increase in human CD45+ lymphocytes in tumor tissue. Animal Model: Male CD-1 mice[1] Dosage: 10 mg/kg Administration: IV; single dose Result: Had the terminal elimination half-life of >14 days.

[1]. Marlon J Hinner, et al. Tumor-Localized Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific Antibody-Anticalin Fusion PRS-343. Clin Cancer Res. 2019 Oct 1;25(19):5878-5889.  

[2]. G. Ku, et al. 525O A phase I dose escalation study of PRS-343, a HER2/4-1BB bispecific molecule, in patients with HER2-positive malignancies. ABSTRACT ONLY, VOLUME 31, SUPPLEMENT 4, S462-S463, SEPTEMBER 01, 2020.