Grants and Contracts Details
Description
Abstract
T-cell immune therapies such as Chimeric Antigen Receptor (CAR) T-cell and Immune
Checkpoint Blockade (ICB) have experienced limited success in B-cell Chronic Lymphocytic
Leukemia (CLL). While anti-CD19 CAR T-cells are extremely effective in other B-cell
malignancies, complete response rates remain low in CLL. T-cell dysfunctionality is well
documented in CLL patients, and CLL cells play an active role in downregulating immune
responses including the production of immune suppressive cytokines like Interleukin-10 (IL-10).
In our recently submitted manuscript, we discovered that suppressing CLL-derived IL-10 greatly
improves responses to ICB in a murine CLL model, and that reducing IL-10 levels restored T-
cell functionality. Others have previously shown positive outcomes with CAR T-cell therapy in
CLL may be linked to proinflammatory cytokine signals, such as IL-6. Therefore, we hypothesize
that CLL-derived IL-10 plays an active role in decreasing CAR T-cell functionality, and we will
test whether IL-10 blockade can restore CAR T-cell function. We will approach this by
generating IL-10 receptor knockout anti-CD19 murine CAR T-cells, and test for increased
functionality, reversal of exhaustion, and improved control of disease. These studies may
greatly impact the treatment of hematologic malignancies, particularly those associated with
immune dysfunction.
Status | Finished |
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Effective start/end date | 10/1/21 → 1/28/22 |
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