15 May 2018

The outcome of a new study may help predict how patients with advanced chronic lymphocytic leukaemia (CLL) will respond to chimeric antigen receptor (CAR) T cell therapy, it has been announced. 

A team from University of Pennsylvania Perelman School of Medicine, USA, investigated the reasons why some of these patients respond poorly to CAR T cell therapy. 

They found that CLL patients with a subset of vital, healthier T cells prior to therapy, tended to have a partial or complete clinical response to the treatment. Those without this subset of cells tended not to respond. 

The team add that these healthier "early memory" T cells were marked by the expression of CD8 and CD27, as well as the absence of CD45RO. Full details were published in Nature Medicine

First author, Dr Joseph Fraietta, says: "With a very robust biomarker like this, we can take a blood sample, measure the frequency of this T cell population, and decide with a degree of confidence whether we can apply this therapy and know the patient would have a response. 

"The ability to select patients most likely to respond would have tremendous clinical impact, as this therapy would be applied only to patients most likely to benefit, allowing patients unlikely to respond to pursue other options. 

"Pre-existing T cell qualities have previously been associated with poor clinical response to cancer therapy, as well differentiation in the T cells," he added. "What is special about what we have done here is finding that critical cell subset and signature." 

Source: Fraietta, J.A., Lacey, S.F., Orlando, E.J., Pruteanu-Malinici, I., Gohil, M., Lundh, S., Boesteanu, A.C., Wang, Y., O’Connor, R.S., Hwang, W.T. and Pequignot, E., 2018. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nature medicine, p.1.

Link: https://www.nature.com/articles/s41591-018-0010-1


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