Covid 19: Improving CAR T Cell Function in CLL by Blocking Interleukin-10

  • Rivas, Jacqueline (PI)

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.
StatusFinished
Effective start/end date10/1/211/28/22

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