New Biomarker May Indicate Success of CAR T-cell Response in Lymphoma Patients

Article

At leukapheresis, a low frequency of differentiated CD3+CD27-CD28--T cells can indicate favorable response to CAR T-cell therapy.

Investigators identified a highly potent biomarker, CD3+CD27-CD28--T cells, which may help identify the lymphoma patients who can most benefit from chimeric antigen receptor (CAR) T-cell therapy before infusion. The findings were published in the journal Frontiers in Immunology.1,2

"The low frequency of differentiated (exhausted) CD3+CD27-CD28--T cells at the time of leukapheresis represents a new blood biomarker that can be used even before the start of CAR-T cell production and infusion and predicts the response to treatment with CAR-T cells in patients,” said study leader Winfried Pickl, Institute of Immunology, Medical University of Vienna, in a press release.1

The 5-year survival rates of diffuse large B cell lymphoma (DLBCL)—the most common form of non-Hodgkin lymphoma—rests between 55% and 64%. Some patients do not respond to combined antibody chemotherapy though, and others have early relapse of DLBCL—these patients tend to have a worse outcome.1

CAR T-cell therapy uses the body’s own T lymphocytes (T cells) as an effective means of fighting against cancer. The therapy equips a patient’s T cells with the specific CARs needed to defend against the necessary lymphatic cancer cells, then returns the optimized cells to the patient’s body.1

Investigators wanted to understand how patient’s T cells function, beginning by measuring the amount of T cells in a patient with lymphoma. The team found that lymphoma patients are deficient in T cells (T cell lymphopenia), which has a more abundant presence of “exhausted” T cells.1

“Our study shows how important the nature of the T cells is for CAR-T cell production and that exhausted T cells, which can be found in a considerable proportion of patients, pose a problem for subsequent CAR-T cell therapy," Pickl said in a press release.1

They were then able to create a methodology for dividing patients based on the high or low probability that they will have a response to CAR T-cell therapy.1

“Our observations of the mode of action of the differently exhausted T cells, which were used as starting material for the production of CAR-T cells, show that the degree of differentiation does not have a negative influence on the direct killing of cancer cells by CAR-T cells, but it does have a negative influence on the leukemia cell-dependent growth and the factor production of the CAR-T cells,” Pickl said in the press release.1

There are some limitations to the study. The first is that the team was unable to get a validated flow cytometric assay, which can monitor CAR T cell expansion in vivo. Additionally, the sample size was small at 33 patients. Further, the team was not able to test CAR T cells in vitro.2

Pickl explained that removing the biomarker cells from the leukapheresis product before beginning to produce CAR-T cells, “could significantly improve the success of therapy even in patients with an unfavorable initial situation."1

Reference

  1. Medical University of Vienna. New biomarker for early prediction of response to CAR-T cell therapy. News Release. January 9, 2023. Accessed on January 23, 2023. https://www.sciencedaily.com/releases/2023/01/230109112811.htm
  2. Worel N, Grabmeier-Pfistershammer K, Kratzer B, et al. The frequency of differentiated CD3+CD27-CD28- T cells predicts response to CART cell therapy in diffuse large B-cell lymphoma. Front. Immunol., 2023. Volume 13 - 2022. doi.org/10.3389/fimmu.2022.1004703

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