Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model

Julie A. Zorn
Bristol Myers Squibb
February 22, 2022
Sci Rep
https://pubmed.ncbi.nlm.nih.gov/35241687

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/35241687

Research summary

The study presents a novel immunocompetent mouse model with a strategically humanized CD3 epitope that enables in vivo evaluation of human CD3-targeting T-cell engagers. The model preserves normal T-cell development and supports effective testing of bispecific T-cell engagers, showing specific T-cell-mediated depletion of B cells in vivo.

Key outcome of the study

Maintains full immune competence while enabling preclinical testing of anti-human CD3 T-cell engagers; demonstrates potent B cell depletion with CD3/CD20 bispecific antibody.

Mouse model

Humanized CD3ε epitope Knockin (hCD3E-epi) mouse model generated by genOway, with a human epitope sequence replacing the murine N-terminal CD3ε region, enabling recognition by clinical anti-hCD3 antibodies.

TARGET:
CD3E
CD3 epsilon chain

Keywords

Immuno-oncology, T-cell engagers, CD3-targeting bispecific antibodies, Preclinical immunotherapy

Technical specifications

Humanized Knockin model, CD3ε epitope substitution, Immunocompetent background, T-cell engager evaluation

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