Fig. 6: XPAT protein protease-cleavable linkers show minimal cleavage in vivo in healthy NHPs. | Nature Cancer

Fig. 6: XPAT protein protease-cleavable linkers show minimal cleavage in vivo in healthy NHPs.

From: Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors

Fig. 6

a, Mean plasma concentrations (±s.d.) following a single i.v. administration of HER2-XPAT protein (single plasma samples from n = 6 NHPs) and HER2-XPAT-NoClvSite (n = 4 NHPs) within one single experiment. b, Plasma concentrations of HER2-XPAT(1x−N) and HER2XPAT(1x−C) relative to the entire HER2-XPAT protein, following a single i.v. dose of HER2-XPAT protein (25 mg kg−1, n = 4 NHPs; 42 mg kg−1, n = 4 NHPs) within one single experiment. c, Quantification of cleavage products with a similar molecular weight to the uTCE generated following incubation of fluorescent-labeled HER2-XPAT protein in plasma from cancer patients (n = 11), patients with inflammatory diseases (n = 27), healthy donors (n = 4) and NHPs (with (n = 6) and without (n = 4) drug-induced inflammation). The plasma incubation experiment represents a closed system with no clearance mechanisms and will therefore overestimate the accumulation of cleavage products occurring in vivo. Horizontal bars represent median values; dots represent individual observations. P values are based on unpaired t-tests.

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