Targeting CEA in metastatic triple negative breast cancer with image-guided radiation followed by Fab-mediated chimeric antigen receptor (CAR) T-cell therapy.

ABSTRACT:

Introduction

Although CAR-T cell therapy has limited efficacy against solid tumors, it has been hypothesized that prior treatment with Image-Guided Radiation Therapy (IGRT) would increase CAR-T cell tumor infiltration, leading to improved antigen specific expansion of CAR-T cells.

Methods

To test this hypothesis in a metastatic triple negative breast cancer (TNBC) model, we engineered two anti-CEA single-chain Fab (scFab) CAR-T cells with signaling domains from CD28zeta and 4-1BBzeta, and tested them in vitro and in vivo.

Results

The anti-CEA scFab CAR-T cells generated from three different human donors demonstrated robust in vitro expression, expansion, and lysis of only CEA-positive TNBC cells, with the CD28z-CAR-T cells showing the highest cyto

SUBMITTER: Aniogo E 

PROVIDER: S-EPMC11695362 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature