Cinrebafusp alfa (PRS 343) is an anticalin-based bispecific drug with high affinity for both CD137/HER2, displaying dissociation constants (Kd) of 0.3 nM to recombinant human HER2 and 5 nM to human monomeric CD137 (4-1BB). It promotes T-cell costimulation via tumor-localized, HER2-mediated 4-1BB clustering and activation, thereby enhancing T-cell receptor-driven responses and facilitating tumor cell eradication. This compound shows promising potential in research concerning HER2-positive solid tumors [1] [2].

HER2:0.3 nM (Kd), 4-1BB:5 nM (Kd)

Cinrebafusp alfa (PRS 343) binds to HER2-expressing MCF-7 cells and CHO cells transfected with human 4-1BB, exhibiting EC50 values of 7.4 nmol/L and 6.2 nmol/L, respectively, as determined by FACS analysis [1].

Cinrebafusp alfa (PRS 343; 0.2-10 mg/kg; administered intravenously; once weekly; for 20 days) showed tumor growth inhibition and a dose-dependent increase in tumor-infiltrating lymphocytes in a humanized mouse model harboring HER2-positive SK-OV-3 tumor cells [1]. In male CD-1 mice, the terminal elimination half-life of Cinrebafusp alfa (10 mg/kg; intravenous administration; single dose) was greater than 14 days. In addition, the terminal elimination half-life of Cinrebafusp alfa (3 mg/kg) administered intravenously as a single dose in male choristoderes monkeys is approximately 4 days [1].