Can I read Toxicity Induced by a Bispecific T Cell–Redirecting Protein Is Mediated by Both T Cells and Myeloid Cells in Immunocompetent Mice on EtoBox?

Toxicity Induced by a Bispecific T Cell–Redirecting Protein Is Mediated by Both T Cells and Myeloid Cells in Immunocompetent Mice by Godbersen-Palmer, Claire; Coupet, Tiffany A.; Grada, Zakaria; Zhang, Samuel C.; Sentman, Charles L. is a Immunology and Microbiology article available to read on EtoBox.

What is Toxicity Induced by a Bispecific T Cell–Redirecting Protein Is Mediated by Both T Cells and Myeloid Cells in Immunocompetent Mice about?

Bispecific T cell engagers have demonstrated clinical efficacy; however, their use can be accompanied by severe toxicity. Mechanistic understanding of these toxicities is limited by a lack of suitable immunocompetent preclinical models. In this study, we describe an immunocompetent mouse tumor model that exhibits bispecific T cell engager-induced toxicity and recapitulates key features similar to those in human cytokine release syndrome. In this study, toxicity occurred between the second and fourth injections of an NK Group 2D bispecific T cell engager protein. Symptoms were transient, peaking 3-4 h after treatment and resolving by 8 h. Mice developed weight loss, elevated plasma cytokines, a significant reduction in spleen white pulp, and lymphocyte infiltration in the liver. Systemic cellular immune changes also occurred; notably, an increase in CD8 + T cell activation, an increase in myeloid cells in the blood, and a population of Ly-6C int monocytes (CD11b + Ly-6G 2 F4/80 2 ) emerged in the liver and spleens of bispecific protein-treated mice. IFN-g was primarily produced by CD8 + T cells in the spleen and was required for the observed changes in both T cell and myeloid popula

Who reads Toxicity Induced by a Bispecific T Cell–Redirecting Protein Is Mediated by Both T Cells and Myeloid Cells in Immunocompetent Mice?

Author

Godbersen-Palmer, Claire; Coupet, Tiffany A.; Grada, Zakaria; Zhang, Samuel C.; Sentman, Charles L.

Publisher

American Association of Immunologists; The American Association of Immunologists (ISSN 0022-1767)

Published

2020

Language

EN

Field

Immunology and Microbiology (Life Sciences)