Biodistribution and activation of next-generation BiTE® molecules in mouse tumor models.

The promise of the BiTE® (bispecific T-cell engager) platform is being realised from the first approval of the CD19 x CD3 BiTE® molecule blinatumomab about 6 years ago to recent data demonstrating clinical activity of BiTE® molecules against additional targets in multiple tumor indications, including first evidence for clinical activity in solid tumors with the PSMA x CD3 BiTE® AMG 212 (Hummel et al., 2020). Development of BiTE® molecules in solid tumors has been challenging due to on-target toxicity in normal tissues, such as gastrointestinal adverse events observed by treatment with the EpCAM BiTE®, AMG 110, in patients (Kebenko et al., 2018).

In previous collaboration studies, human and mouse surrogate short half-life BiTE® molecules have been investigated. Recently, the biodistribution of a mouse surrogate half-life extended BiTE® molecule targeting mesothelin has also been evaluated (Suurs et al., 2021).

The biodistribution of next generation BiTE® molecules in vivo deserves more characterisation. The goal of this collaboration is to further investigate the biodistribution/localisation of next generation BiTE® molecules directed against solid tumor targets in mouse tumor models.

Radiolabeling of antibody therapeutics can be used to evaluate tumor targeting, tissue biodistribution, and pharmacokinetics (Waaijer et al., 2018).