Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model

Oncoimmunology. 2017 Jun 20;6(10):e1342909. doi: 10.1080/2162402X.2017.1342909. eCollection 2017.


The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model.

Keywords: Chimeric antigen receptors; immune checkpoints; immunoevasion; prostate stem cell antigen; solid tumors; targeting module.

Publication types

  • Research Support, Non-U.S. Gov't