Brogdon, Jennifer, Pruteanu-Malinici, Iulian, Melenhorst, J. Joseph, June, Carl H., Fraietta, Joseph A., Young, Regina M., Levine, Bruce L. and Lacey, Simon F. (2021) Decade-long Remissions of Leukemia Sustained by the Persistence of Activated CD4 CAR T Cells. Science translational medicine.

Abstract

The adoptive transfer of T cells reprogrammed to target tumor cells has demonstrated significant potential in various malignancies. However, little is known about the long-term memory potential and the clonal stability of the infused cells. Here, we studied the fate of CD19 redirected chimeric antigen receptor (CAR19) T-cells in two leukemia patients who achieved and sustained a complete remission almost a decade ago. CAR T cells were still detectable 9+ years post-infusion. Surprisingly, a prominent, highly activated CD4+ population developed in both subjects in the years post-infusion, dominating the CAR T cell population at the late time points. This transition was reflected in the stabilization of the clonal make-up of CAR T cells with a repertoire dominated by few clones. Single-cell profiling of CAR T-cells obtained 9 years post-infusion demonstrated that these long-persisting CD4+ CAR T cells exhibited cytotoxic characteristics along with strong evidence of ongoing functional activation and proliferation. Given data that CD19 directed CAR T with a CD28 signaling domain do not persist long term, our data provide important insight into the development of long-term anti-tumor responses necessary for sustained remission in leukemia following CAR T-cell therapy.

Item Type:	Article
Keywords:	Deep remission of leukemia, CD4 CAR T-cells, single cell profiling, CYTOF
Date Deposited:	23 Jun 2021 00:45
Last Modified:	23 Jun 2021 00:45
URI:	https://oak.novartis.com/id/eprint/44746