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.
Cinrebafusp alfa (PRS 343) binds HER2-expressing MCF-7 cells with an EC50 of 7.4 nmol/L and binds to CHO cells transfected with human 4-1BB with an EC50 of 6.2 nmol/L in a FACS assay[1].
Cinrebafusp alfa (PRS 343; 0.2-10 mg/kg; IV; once weekly; for 20 day) leads to tumor growth inhibition and has a dose-dependent increase of tumor-infiltrating lymphocytes in a humanized mouse model engrafted with HER2-positive SK-OV-3 tumor cells[1]. Cinrebafusp alfa (10 mg/kg; IV; single dose) has the terminal elimination half-life of >14 days in male CD-1 mice. Cinrebafusp alfa (3 mg/kg; IV; single dose) has the terminal elimination half-life approximately 4 days in male cynomolgus monkeys[1].
References:
[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.