T cells expressing chimeric antigen receptor promote immune tolerance
Antonio Pierini, Bettina P Iliopoulou, Heshan Peiris, Magdiel Pérez-Cruz, Jeanette Baker, Katie Hsu, Xueying Gu, Ping-Ping Zheng, Tom Erkers, Sai-Wen Tang, William Strober, Maite Alvarez, Aaron Ring, Andrea Velardi, Robert S Negrin, Seung K Kim, Everett H Meyer, Antonio Pierini, Bettina P Iliopoulou, Heshan Peiris, Magdiel Pérez-Cruz, Jeanette Baker, Katie Hsu, Xueying Gu, Ping-Ping Zheng, Tom Erkers, Sai-Wen Tang, William Strober, Maite Alvarez, Aaron Ring, Andrea Velardi, Robert S Negrin, Seung K Kim, Everett H Meyer
Abstract
Cellular therapies based on permanent genetic modification of conventional T cells have emerged as a promising strategy for cancer. However, it remains unknown if modification of T cell subsets, such as Tregs, could be useful in other settings, such as allograft transplantation. Here, we use a modular system based on a chimeric antigen receptor (CAR) that binds covalently modified mAbs to control Treg activation in vivo. Transient expression of this mAb-directed CAR (mAbCAR) in Tregs permitted Treg targeting to specific tissue sites and mitigated allograft responses, such as graft-versus-host disease. mAbCAR Tregs targeted to MHC class I proteins on allografts prolonged islet allograft survival and also prolonged the survival of secondary skin grafts specifically matched to the original islet allograft. Thus, transient genetic modification to produce mAbCAR T cells led to durable immune modulation, suggesting therapeutic targeting strategies for controlling alloreactivity in settings such as organ or tissue transplantation.
Conflict of interest statement
Conflict of interest: The authors have declared that no conflict of interest exists.
Figures
![Figure 1. mAbCAR construct and its expression…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g001.jpg)
![Figure 2. mAbCAR-expressing T cells are activated…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g002.jpg)
![Figure 3. Tissue-specific FITC mAbs modulate mAbCAR…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g003.jpg)
![Figure 4. mAbCAR Tregs retain phenotype and…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g004.jpg)
![Figure 5. FITC-H-2D d -mAbCAR Tregs induce…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g005.jpg)
![Figure 6. FITC-H-2D d -mAbCAR Tregs home…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g006.jpg)
![Figure 7. FITC-H-2D d -mAbCAR Tregs acquire…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5846896/bin/jciinsight-2-92865-g007.jpg)
Source: PubMed