08 February 2022

CAR T cells are detectable and functionally active at least a decade after infusion, a new US study has found.

Two patients with chronic lymphocytic leukaemia (CLL) volunteered in 2010 to become the first participants in a clinical trial of an experimental therapy at the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania. Now a new analysis has looked at these patients’ sustained remission.

The treatment, which eradicated their end-stage leukaemia, helped to introduce a new era of highly personalised medicine. CAR T cell therapy has been extremely effective for specific leukaemias and lymphomas, and researchers are also looking at their impact on solid tumours.

In their study, published in Nature, the Penn researchers and colleagues from Children’s Hospital of Philadelphia found an evolution in the CAR T cells over time, with a highly activated CD4+ population emerging and becoming dominant in both patients. This suggests two phases to CAR T cell therapy – an initial phase of activity dominated by CD8+ cells, followed by long-term remission controlled by CD4+ cells.

First author Professor Joseph Melenhorst, a research professor of pathology and laboratory medicine at Penn, said: “This long-term remission is remarkable, and witnessing patients living cancer-free is a testament to the tremendous potency of this ‘living drug’ that works effectively against cancer cells.”

CLL, the first cancer in which CAR T cells were studied and used at Penn, is the most common type of leukaemia in adults. While treatment has improved, it remains incurable with standard approaches.

Senior author Professor Carl June, the Richard W. Vague professor in immunotherapy in pathology and laboratory medicine at Penn, said: “Penn has begun testing next-generation T cells in more blood cancers, including lymphomas, and against the challenging solid tumour cancers.

“A considerable amount of deep learning goes into studies that will fine tune the way cancer patients are treated with CAR T cells, and we look forward to the next phase of research and enhancements, including how best to use this approach to target other cancers and diseases.”

Source:

Melenhorst JJ, Chen GM, Wang M, Porter DL, Chen C, Collins MA, Gao P, Bandyopadhyay S, Sun H, Zhao Z, Lundh S, Pruteanu-Malinici I, Nobles CL, Maji S, Frey NV, Gill SI, Tian L, Kulikovskaya I, Gupta M, Ambrose DE, Davis MM, Fraietta JA, Brogdon JL, Young RM, Chew A, Levine BL, Siegel DL, Alanio C, Wherry EJ, Bushman FD, Lacey SF, Tan K, June CH. (2022) “Decade-long leukaemia remissions with persistence of CD4+ CAR T cells.” Nature, doi: 10.1038/s41586-021-04390-6

Link: https://www.nature.com/articles/s41586-021-04390-6

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