Regeneron’s humanized mice for therapeutic TCR discovery; plus Pattern, Century and more

In Science Immunology,  Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) demonstrated how its VelociT humanized mouse model platform could enable de novo discovery of fully human therapeutic TCRs. Using the company's VelociGene technology, researchers led by Lynn Macdonald replaced mouse TCRA and TCRB variable regions, along with ectodomain regions of four other genes, with human sequences to generate 'VelociT' mice. In a validation experiment, the team isolated and screened TCRs from VelociT mice immunized with human tumor-associated peptide antigens, yielding a TCR that showed antitumor activity in a xenograft mouse model of melanoma.

The team said that while other models have humanized portions of TCR expression, regulation or selection in mice, CD4- and CD8-driven immunity has never been combined into one model. ...