| Autor: |
Melenhorst, J. Joseph, Chen, Gregory M., Wang, Meng, Porter, David L., Chen, Changya, Collins, McKensie A., Gao, Peng, Bandyopadhyay, Shovik, Sun, Hongxing, Zhao, Ziran, Lundh, Stefan, Pruteanu-Malinici, Iulian, Nobles, Christopher L., Maji, Sayantan, Frey, Noelle V., Gill, Saar I., Tian, Lifeng, Kulikovskaya, Irina, Gupta, Minnal, Ambrose, David E., Davis, Megan M., Fraietta, Joseph A., Brogdon, Jennifer L., Young, Regina M., Chew, Anne, Levine, Bruce L., Siegel, Donald L., Alanio, Cécile, Wherry, E. John, Bushman, Frederic D., Lacey, Simon F., Tan, Kai, June, Carl H. |
| Zdroj: |
Nature; 20220101, Issue: Preprints p1-7, 7p |
| Abstrakt: |
The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers1–7. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia1–4who achieved a complete remission in 2010. CAR T cells remained detectable more than ten years after infusion, with sustained remission in both patients. Notably, a highly activated CD4+population emerged in both patients, dominating the CAR T cell population at the later time points. This transition was reflected in the stabilization of the clonal make-up of CAR T cells with a repertoire dominated by a small number of clones. Single-cell profiling demonstrated that these long-persisting CD4+CAR T cells exhibited cytotoxic characteristics along with ongoing functional activation and proliferation. In addition, longitudinal profiling revealed a population of gamma delta CAR T cells that prominently expanded in one patient concomitant with CD8+CAR T cells during the initial response phase. Our identification and characterization of these unexpected CAR T cell populations provide novel insight into the CAR T cell characteristics associated with anti-cancer response and long-term remission in leukaemia. |
| Databáze: |
Supplemental Index |
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