Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model
iScience, ISSN: 2589-0042, Vol: 27, Issue: 2, Page: 108879
2024
- 7Citations
- 11Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations7
- Citation Indexes7
- CrossRef6
- Captures11
- Readers11
- 11
Article Description
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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S2589004224001007; http://dx.doi.org/10.1016/j.isci.2024.108879; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85184046452&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/38327771; https://linkinghub.elsevier.com/retrieve/pii/S2589004224001007; https://dx.doi.org/10.1016/j.isci.2024.108879
Elsevier BV
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