Figure 2.

Rational optimization of anti-CD3 H2B4 to reduce polyreactivity and clipping. (a) Rational IgG variants with retained binding demonstrated lower polyreactivity (DNA score) compared to the parental 2B5 while maintaining desired affinity as measured by Biacore. (b) Re-humanization to H2B5 as T-BsAb with a stable control binding arm minimized clipping compared to H2B4, while H2B5v6 showed further clipping reduction as measured by cGE. Red arrows indicate clipped species. (c) H2B5v6 T-BsAb demonstrated reduced but acceptable in vitro CTL activity compared to re-humanized H2B5