학술논문
Decade-long leukaemia remissions with persistence of CD4+CAR T cells
Document Type
Article
Author
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.
Source
Nature; 20220101, Issue: Preprints p1-7, 7p
Subject
Language
ISSN
00280836; 14764687
Abstract
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.