Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.
Publication/Presentation Date
5-1-2018
Abstract
One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells
Volume
6
Issue
5
First Page
509
Last Page
516
ISSN
2326-6074
Published In/Presented At
Magee, M. S., Abraham, T. S., Baybutt, T. R., Flickinger, J. C., Jr, Ridge, N. A., Marszalowicz, G. P., Prajapati, P., Hersperger, A. R., Waldman, S. A., & Snook, A. E. (2018). Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases. Cancer immunology research, 6(5), 509–516. https://doi.org/10.1158/2326-6066.CIR-16-0362
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
29615399
Department(s)
Administration and Leadership
Document Type
Article