Bispecific Antibodies Enable Synthetic Agonistic Receptor-Transduced T Cells for Tumor Immunotherapy.

ABSTRACT:

Purpose

Genetically engineered T cells are powerful anticancer treatments but are limited by safety and specificity issues. We herein describe an MHC-unrestricted modular platform combining autologous T cells, transduced with a targetable synthetic agonistic receptor (SAR), with bispecific antibodies (BiAb) that specifically recruit and activate T cells for tumor killing.

Experimental design

BiAbs of different formats were generated by recombinant expression. T cells were retrovirally transduced with SARs. T-cell activation, proliferation, differentiation, and T-cell-induced lysis were characterized in three murine and human tumor models in vitro and in vivo.

Results

Murine T cells transduced with SAR composed of an extracellular domain EGFRvIII fused to

SUBMITTER: Karches CH 

PROVIDER: S-EPMC7611266 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature