Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice (original) (raw)
ADS
;
- Dougan, Michael ;
- Jailkhani, Noor ;
- Ingram, Jessica ;
- Fang, Tao ;
- Kummer, Laura ;
- Momin, Noor ;
- Pishesha, Novalia ;
- Rickelt, Steffen ;
- Hynes, Richard O. ;
- Ploegh, Hidde
Abstract
Despite its success in treating hematological cancers, chimeric antigen receptor (CAR) T cell therapy does not so easily eliminate solid tumors. Solid tumors generally develop in a highly immunosuppressive environment and are difficult to target, mostly due to a lack of tumor-specific antigen expression, but other factors contribute as well. This study develops a strategy to target multiple solid tumor types through markers in their microenvironment. The use of single-domain antibody (VHH)-based chimeric antigen receptor (CAR) T cells that recognize these markers circumvents the need for tumor-specific targets. VHH-based CAR T cells that target the tumor microenvironment through immune checkpoint receptors or through stroma and ECM markers are effective against solid tumors in syngeneic, immunocompetent animal models.
Publication:
Proceedings of the National Academy of Science
Pub Date:
April 2019
DOI:
Bibcode: