Release date: 2018-05-07
Professor Carl H. June of the University of Pennsylvania is recognized as a "big cow" in the CAR-T field. Recently, a recent paper he published published a T-cell biomarker that predicts how patients with chronic lymphocytic leukemia will respond to CAR-T therapy. Preliminary validation studies in a small number of patients have shown that the marker has a prediction accuracy of up to 100%.
In recent years, the development of CAR-T therapy has subverted the treatment of some blood cancers. However, although 80% of patients with acute lymphoblastic leukemia (ALL) who are treated with CAR-T cell therapy (Kymriah) are able to produce a significant response, in clinical trials, only 26% of advanced chronic lymphocytes Patients with chronic lymphocytic leukemia (CLL) respond to this type of therapy.
On April 30, published in the journal Nature Medicine, entitled "Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia, scientists from the University of Pennsylvania may have found some The reason why patients with advanced CLL do not respond to CAR-T cell therapy.
Key T cell subset
Studies have shown that patients with CLL who have a vital, healthier T cell subset before receiving CAR-T cell therapy have a partial or complete clinical response to treatment, whereas patients who lack these T cells do not respond to CAR. -T therapy.
At the same time, a team led by Dr. J. Joseph Melenhorst and Dr. Joseph A. Fraietta found that these healthier "early memory" T cells are marked by the expression of CD8 and CD27 and the lack of CD45RO. They also validated this feature in a small number of patients and predicted which patients would achieve complete remission with 100% accuracy.
CAR T cells ready for infusion. Credit: Penn Medicine
Specific research
Specifically, in this new study, scientists retrospectively reviewed 41 advanced, highly pre-treated high-risk CLL patients who received at least one dose of CAR targeting CN19. -T therapy.
In several experiments, the team compared the gene expression profiles and phenotypes of T cells in patients who were fully, partially, and unresponsive to CAR-T therapy. The results of the analysis showed that CAR-T cells persisting and expanding in complete responders are rich in genes that regulate early memory and effector T cells and have IL-6/STAT3 characteristics (IL-6 in early T cells) The increase in the level of the /STAT3 signaling pathway is related to the patient's clinical response to CAR-T therapy, and the genes expressed by non-responders are associated with advanced T cell differentiation, glycolysis, depletion, and apoptosis.
To validate these biomarkers, the researchers screened early memory T cells from 8 CLL patients before and after CAR-T treatment. In the end, they identified a complete responder with 100% specificity and sensitivity.
Dr. Fraietta said: "Previous studies have shown that pre-existing T cell quality is associated with poor clinical response. The special feature of our study is the identification of key cell subsets and features. With such a very robust Biomarkers, we can collect blood samples from patients, measure the incidence of such T cell populations, and decide whether to use CAR-T therapy for patients. The ability to screen patients most likely to respond to treatment has a huge Clinical impact, because, in this way, patients who are unlikely to respond to such treatments can seek other options as early as possible."
Significance
In summary, the authors believe that this new finding not only points to a new T-cell biomarker as a "much-needed patient-selection tool" but also in the implementation of CAR-T cell therapy. Improving the immunological health of patients through "emerging cell production techniques" has given rise to opportunities.
However, the researchers also said that they are still unclear why some patients' T cells are "less ideal" than T cells in other patients before treatment, and whether this biomarker can be extended to other cancer types, especially entities. tumor. In the future, clinical studies involving more CLL patients will help answer these questions.
Reference materials:
T cell biomarker predicts which CLL patients will respond to CAR T cell therapy
Source: Bio-Exploration
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