Download MendeleyPharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody.
Al-Khami, A.A., Youssef, S., Abdiche, Y., Nguyen, H., Chou, J., Kimberlin, C.R., Chin, S.M., Kamperschroer, C., Jessen, B., Kern, B., Budimir, N., Dillon, C.P., Xu, A., Clark, J.D., Chou, J., Kraynov, E., Rajpal, A., Lin, J.C., Salek-Ardakani, S.(2020) Mol Cancer Ther 19: 2105-2116
- PubMed: 32847983
- DOI: https://doi.org/10.1158/1535-7163.MCT-20-0093
- Primary Citation of Related Structures:
6XKR - PubMed Abstract:
Development of antagonistic mAbs that specifically target the immune checkpoint receptor, programmed cell death protein-1 (PD-1), is of great interest for cancer immunotherapy. Here, we report the biophysical characteristics and nonclinical antagonistic activities of sasanlimab (PF-06801591), a humanized anti-PD-1 antibody of IgG4 isotype. We show that sasanlimab binds selectively and with similar high potency to human and cynomolgus monkey PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, with no detectable Fc-dependent effector function. The binding of sasanlimab to human and cynomolgus PD-1 is associated with the formation of a stable complex, which is likely to be the main driver of this high-affinity interaction. In vitro , sasanlimab significantly augmented T-cell proliferation and cytokine production in mixed lymphocyte reaction and superantigen stimulation assays. In vivo , sasanlimab accelerated the incidence of GvHD by enhancing T-cell proliferation and cytokine secretion in a xenogeneic model of acute GvHD and halted the growth of MC-38 colon adenocarcinoma tumors in human PD-1 knock-in mice. Pharmacokinetic and toxicokinetic findings from cynomolgus monkey showed that sasanlimab was active and well-tolerated. Taken together, the data presented here support the clinical development of sasanlimab for the treatment of patients with advanced cancers as a single agent or in combination with other immunotherapies.
Organizational Affiliation:
Cancer Immunology Discovery, Pfizer Inc., San Diego, California.
