Existing drugs may help improve the response to advanced leukemia cell therapy

Today in an online report in the Journal of Clinical Research, the team demonstrated how this drug called JQ1 can improve CAR-T cell function by inhibiting the bromine domain and extra terminal (BET) protein

These findings prove for the first time this resistance mechanism and provide a much-needed target for CLL when using cell therapies such as CAR to treat patients

"Why car T cells cannot completely attack cancer cells in many patients with chronic lymphocytic leukemia is an important question that needs to be answered in order to expand the use of these immunotherapies in chronic lymphocytic leukemia and other cancers," said senior author Joseph A.

Using small molecule inhibitors and T cells and CD19 CAR-T cells from multiple previously treated patients, the researchers demonstrated that the BET protein plays a role in down-regulating CAR expression.

During the successful treatment of CLL, the use of JQ1 treatment also increased the levels of various immunomodulatory cytokines and chemokines produced by CAR-T cells previously reported

In view of the observation that BET inhibition can rejuvenate CAR-T cells in dysfunctional CLL patients, the authors suggest that JQ1 be incorporated into the cell engineering and expansion process, which can produce fewer defects and more effective final CAR-T cells for patients

The extent to which the above-mentioned pathway contributes to the effect of JQ1 on CAR-T cells is the focus of the research team's ongoing research

"This work shows us that T cells can learn new skills," said Dr.

This work was supported by the Bob Levis Foundation Group, National Institute of Allergy and Infectious Diseases (T32 AI007632), National Cancer Institute (P01 CA214278 575, R01 CA241762 U54 CA244711 576, P30 CA016520-44S3, and P30 CA016520-44S4) ), the National Institute of Aging (U01 AG066100), the National Institute of Allergy and Infectious Diseases (T32 AI007632), and the National Cancer Institute (P01 CA214278 575, R01 CA241762 U54 CA244711 576, P30 CA016520-44S4)

Journal Reference :

1. Weimin Kong, Alexander Dimitri, Wenliang Wang, In-Young Jung, Christopher J.