Description

A Novel T-cell Engaging Bispecific Antibody Platform Developed Using Sequence-based Discovery in Unique Transgenic Rats

Starlynn Clarke, Duy Pham, Shelley Force Aldred, Nathan Trinklein, Ute Schellenberger, Katherine Harris, Kevin Dang, Payal Pratap, Harshad Ugamraj, Marianne Bruggemann, and Wim vanSchooten

TeneoBio, 1490 O’Brien Drive, Menlo Park, CA

We have developed a system for the rapid identification of high affinity, fully human single domain antibodies (UniDabs™) through sequence-based discovery in unique transgenic Rats (UniRat™). UniRats express a comprehensive human VH gene repertoire in a heavy chain only antibody format and mount robust immune responses to a wide variety of antigens. Heavy chain only antibodies identified by high-throughput functional screening can be converted to single domain UniDabs that maintain their original binding properties as multivalent proteins or as Fc fusions. This versatility allows for the creation of multi-specific proteins targeting one or more antigens with pM affinities. By combining a tumor-specific UniDab with a T cell engagement domain we have leveraged the flexibility of these molecules and generated a novel platform for bispecific cancer therapeutics. The primary advantage of our design is its modularity which allows for independent calibration of both the T cell recruitment and tumor targeting domains. The resulting molecules mediate potent and specific tumor cell lysis through recruitment and activation of T cells.