American Association for Cancer Research
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15357163mct200093-sup-237007_3_supp_6400465_qcvdjp.pdf (83.89 kB)

Figure S15 from Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody

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posted on 2023-04-03, 18:28 authored by Amir A. Al-Khami, Sawsan Youssef, Yasmina Abdiche, HoangKim Nguyen, Joyce Chou, Christopher R. Kimberlin, Sherman M. Chin, Cris Kamperschroer, Bart Jessen, Brent Kern, Natalija Budimir, Christopher P. Dillon, Allison Xu, Jerry D. Clark, Jeffrey Chou, Eugenia Kraynov, Arvind Rajpal, John C. Lin, Shahram Salek-Ardakani

Supplementary Figure 15 shows no body weight changes in response to sasanlimab treatment in mice.

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ARTICLE 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.