T cells expressing chimeric, antibody based receptor (CART cells or T bodies) recognize their target and execute their destined function in none MHC restricted manner. Effector T bodies lyse their target and secrete effector cytokines whereas regulatory T cells produce suppresive cytokines. In an attempt to optimize the performance of Teff and Treg T bodies, we used murine models with spontanous or induced pathology; mammary cancers in the HER2NG mice, over expressing Her2/neu, or the CEABAC transgenic mice expressing low levels of CEA in its colon. In the first system we found that i.v. injections of Her2/neu Teff T bodies delayed the apperance of mammary tumors. When injected to tumor bearing mice, Tbodies accumulated in the mammary lesion. Yet, to eradicate the tumors, repeated injections were needed. A single intratumoral injection of Teff T bodies rejected large tumors, nevertheless, most tumors relapsed. In the second system, naïve Tregs were modified to express a CEA-specific CAR and transferred into colitic CEA transgenic mice. Colitis was induced by azoxymethane-DSS that develop colitis and later on colorectal tumors. The other colitis model was induced by i.v.injection of CEA-specific Teff T bodies. The adoptive transfer of the Treg T-bodies markedly reduced the severity of colitis as monitored by endoscopy. Moreover, in the AOM-DSS model CEA-Treg T-bodies significantly decreased the subsequent tumor burden.
- Copyright © 2013 by The American Association of Immunologists, Inc.