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TriTACs, a Novel Class of T-Cell–Engaging Protein Constructs Designed for the Treatment of Solid Tumors by Richard J. Austin; Bryan D. Lemon; Wade H. Aaron; Manasi Barath; Patricia A. Culp; Robert B. DuBridge; Luke B. Evnin; Adrie Jones; Anand Panchal; Purbasa Patnaik; Vanitha Ramakrishnan; Sony S. Rocha; Pui Seto; Kenneth Sexton; Kathryn L. Strobel; Russell Wall; Stephen Yu; Timothy Z. Yu; Che-Leung Law; Patrick A. Baeuerle; Holger Wesche is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is TriTACs, a Novel Class of T-Cell–Engaging Protein Constructs Designed for the Treatment of Solid Tumors about?

T cells have a unique capability to eliminate cancer cells and fight malignancies. Cancer cells have adopted multiple immune evasion mechanisms aimed at inhibiting T cells. Dramatically improved patient outcomes have been achieved with therapies genetically reprogramming T cells, blocking T-cell inhibition by cancer cells, or transiently connecting T cells with cancer cells for redirected lysis. This last modality is based on antibody constructs that bind a surface antigen on cancer cells and an invariant component of the T-cell receptor. Although high response rates were observed with T-cell engagers specific for CD19, CD20, or BCMA in patients with hematologic cancers, the treatment of solid tumors has been less successful. Here, we developed and characterized a novel T-cell engager format, called TriTAC (for Trispecific T-cell Activating Construct). TriTACs are engineered with features to improve patient safety and solid tumor activity, including high stability, small size, flexible linkers, long serum half-life, and highly specific and potent redirected lysis. The present study establishes the structure/activity relationship of TriTACs and describes the development of HPN424, a

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Author

Richard J. Austin; Bryan D. Lemon; Wade H. Aaron; Manasi Barath; Patricia A. Culp; Robert B. DuBridge; Luke B. Evnin; Adrie Jones; Anand Panchal; Purbasa Patnaik; Vanitha Ramakrishnan; Sony S. Rocha; Pui Seto; Kenneth Sexton; Kathryn L. Strobel; Russell Wall; Stephen Yu; Timothy Z. Yu; Che-Leung Law; Patrick A. Baeuerle; Holger Wesche

Publisher

American Association for Cancer Research; American Association for Cancer Research (AACR) (ISSN 1535-7163)

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)