Tetravalent biepitopic targeting enables intrinsic antibody agonism of tumor necrosis factor receptor superfamily members.
Yanli Yang, Sherry Yeh, Shravan Madireddi, Wadim L. Matochko, Chen Gu, Patricia Pacheco Sanchez, Mark Ultsch, Gladys de Leon Boenig, Seth F. Harris, Brandon Leonard, Suzie J. Scales, Jing W Zhu, Erin Christensen, Julie Q. Hang, Randall J. Brezski, Scot A. Marsters, Avi Ashkenazi, Siddharth Sukumaran, Henry Chiu, Rafael Cubas, J.M. Kim, Greg A. Lazar
Abstract
cells, obviated the requirement for CD28 co-signal for T cell activation, and enabled superior pharmacodynamic activity relative to native IgG in a murine vaccination model. This work establishes a proof of concept for an engineering approach that addresses a major gap for the therapeutic activation of this important receptor class.
Topics & Concepts
AntibodyReceptorTumor necrosis factor alphaMonoclonal antibodyAgonistCell biologyCancer researchBiologyImmune systemPharmacologyImmunologyBiochemistryMonoclonal and Polyclonal Antibodies ResearchT-cell and B-cell ImmunologyImmunotherapy and Immune Responses