| Autor: |
Yufei Wang, Jae-Won Cho, Gabriella Kastrunes, Alicia Buck, Cecile Razimbaud, Aedin C. Culhane, Jiusong Sun, David A. Braun, Toni K. Choueiri, Catherine J. Wu, Kristen Jones, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Quan Zhu, Sabina Signoretti, Gordon J. Freeman, Martin Hemberg, Wayne A. Marasco |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 2, Pp 108879- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.108879 |
| Popis: |
Summary: One of the major barriers that have restricted successful use of chimeric antigen receptor (CAR) T cells in the treatment of solid tumors is an unfavorable tumor microenvironment (TME). We engineered CAR-T cells targeting carbonic anhydrase IX (CAIX) to secrete anti-PD-L1 monoclonal antibody (mAb), termed immune-restoring (IR) CAR G36-PDL1. We tested CAR-T cells in a humanized clear cell renal cell carcinoma (ccRCC) orthotopic mouse model with reconstituted human leukocyte antigen (HLA) partially matched human leukocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) and bearing human ccRCC skrc-59 cells under the kidney capsule. G36-PDL1 CAR-T cells, haploidentical to the tumor cells, had a potent antitumor effect compared to those without immune-restoring effect. Analysis of the TME revealed that G36-PDL1 CAR-T cells restored active antitumor immunity by promoting tumor-killing cytotoxicity, reducing immunosuppressive cell components such as M2 macrophages and exhausted CD8+ T cells, and enhancing T follicular helper (Tfh)-B cell crosstalk. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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