Blood: Why does CAR-T cell therapy fail in the treatment of some patients with lymphoma?

February 5, 2021 // -- Chimeric antigen-treated T-cell therapy (CAR-T-cell therapy) is a major map for the treatment of a variety of blood cancer therapies, such as acute lymphoblastic leukemia and diffuse large B-cell lymphoma;
researchers from the Moffitt Cancer Research Center have been exploring why some patients respond better to CAR-T cell therapy than others, and what should be done to improve the effectiveness of the treatment.
a recent study published in the international journal Blood, scientists at the Moffitt Cancer Research Center found that immune dysfunction may directly affect the response and efficiency of patients with diffuse large B-cell lymphoma to CAR-T cell therapy.
diffuse large B-cell lymphoma is one of the most common non-Hodgkin's lymphomas, a malignant cancer that affects B-lymphocytes, which are a class of white blood cells in the body that help fight infection; icabtagene ciloleucel is the first CAR-T cell therapy approved by the FDA to treat this type of cancer;
For CAR-T cell therapy, the researchers collected the patient's own immune cells through a single-picking process, then genetically modified them in the lab, adding chisellular antigens to help T cells locate and kill tumor cells in the patient's body.
Photo Source: CC0 Public Domain In this observational study, researchers collected blood and tumor samples from the bodies of 105 patients treated with axicabtagene ciloleucel, and then analyzed the samples separately before and after the patient received treatment;
Researcher Dr Frederick Locke said patients with active large B-cell lymphomas have experienced disorders of the body's immune function, such as elevated levels of myelin in the body and T-cell defects;
-related studies have shown that large tumor tissue can lead to immune dysfunction due to high levels of cytokines in chronic interferon signaling machines in tumors, and in short, CAR-T cell therapy may not be able to function successfully in patients with immune dysfunction, due to impaired growth of CAR-T cells in the patient's body, and because tumors caused by the expression of multiple immune checkpoints can become resistant to CAR-T cell therapy.
Michael Jain, a researcher at the end of the study, said the study could help improve the implementation of CAR-T cell therapy in two ways, starting with the use of interventions to improve the quality of immune cells in the patient's body before single extraction (cell separation) to produce better CAR-T cell products, while also helping the patient's immune system better prepared to accept CAR-T cells to increase the response after cell infusion.
later in the study, researchers needed further research to determine exactly what kind of intervention should be taken and to help modify the therapy to reduce the recurrence of disease in patients who received CAR-T cell therapy.
() Original source: Michael D. Jain, Hua Zhao, Xuefeng Wang, et al. Tumor interferon signaling and suppressive myeloid cells associate with CAR T cell failure in large B cell lymphoma, Blood (2021). DOI:10.1182/blood.2020007445