Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
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
View: Text | PDF
Research Article Immunology Transplantation

T cells expressing chimeric antigen receptor promote immune tolerance

  • Text
  • PDF
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.

Authors

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

×

Figure 3

Tissue-specific FITC mAbs modulate mAbCAR T cell homing and function in vivo.

Options: View larger image (or click on image) Download as PowerPoint
Tissue-specific FITC mAbs modulate mAbCAR T cell homing and function in ...
(A) Targeting mAbCAR T cells regulates homing. The graph shows bioluminescent signal from allogeneic luc+ untransfected Tcons (black), luc+ SDF1-mAbCAR Tcons (blue), or luc+ MAdCAM1-mAbCAR Tcons (red) at day +4, +7, and +12 after transfer in mice that received TCD BM at day 0. One representative of three consecutive experiments is presented; 2–4 mice/group were used in each experiment. ANOVA test with Bonferroni post-test; mean ± SEM; ***P < 0.001. (B) Targeting mAbCAR T cells alters localization. Representative bioluminescent images of mice that received luc+ untransfected Tcons, luc+ SDF1-mAbCAR Tcons, or luc+ MAdCAM1-mAbCAR Tcons at day +12 after transfer. Data are representative of 1 of 3 consecutive experiments. (C) Targeting mAbCAR T cells modulates GvHD. GvHD score over time of recipient mice that received allogeneic untransfected Tcons, SDF1-mAbCAR Tcons, or MAdCAM1-mAbCAR Tcons. One representative of three independent experiments is presented. ANOVA test with Bonferroni post-test; mean ± SEM; ***P < 0.001. (D) mAbCAR T cells mediate graft-versus-tumor effects. Tumor growth analyzed by BLI in lethally irradiated BALB/c mice that received allogeneic C57BL/6 TCD BM and luc+ A20 alone (black), luc+ A20 and allogeneic isotype-mAbCAR Tcons (gray), or luc+ A20 and allogeneic SDF1-mAbCAR Tcons (blue). One representative of two consecutive experiments is reported; at least 3 mice/group were used. Two-tailed Student’s t test; mean ± SEM; ***P < 0.001. (E) mAbCAR T cells eliminate tumor in vivo. Representative bioluminescent images of lethally irradiated BALB/c mice that received allogeneic C57BL/6 TCD BM and luc+ A20 alone, luc+ A20 and isotype-mAbCAR Tcons, or luc+ A20 and SDF1-mAbCAR Tcons at day +7, +14, and +21 after transplant. One representative of two consecutive experiments is reported; at least 3 mice/group were used. (F) SDF1-directed mAbCAR T cells enhance survival. Survival of lethally irradiated BALB/c mice that received irradiation alone (black circle), allogeneic C57BL/6 TCD BM (black squares), TCD BM + luc+ A20 alone (white squares in black), TCD BM + luc+ A20 + allogeneic isotype-mAbCAR Tcons (red triangles), TCD BM + luc+ A20 + allogeneic SDF1-mAbCAR Tcons (white circles in blue). One representative of two consecutive experiments is reported; at least 3 mice/group were used. Log-rank survival test; *P < 0.05 for differences between the groups that received luc+ A20 alone and luc+ A20 + allogeneic SDF1-mAbCAR Tcons.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts