Brady Stein - Northwestern

Brady Stein, Northwestern

Brady Stein MPN ResearcherProject Title:

Anti-PDL1 therapy for patients with Myelofibrosis 

Focus Area:

Application of Immunotherapy to the treatment of Myelofibrosis

Question/Issue:

T-cells, which fight infections, cannot recognize cancer cells. It has been proven that cancer cells have the ability to disguise themselves. A protein known as PDL-1 disguises cancer cells so that T-cells do not recognize the cancer.

Project description:

This project will be a small pilot study using a drug called a PDL-1 inhibitor with 10 patients that will determine if patients respond to anti-PDL1 therapy. If this project is successful, it paves the way to proving that the immune system of MF patients can be restored to attack the cancer cell.

Project abstract:

Myelofibrosis (MF) is characterized by constitutional symptoms, cytopenias, extramedullary hematopoiesis, risk of acute leukemic transformation, and shortened life expectancy. JAK-STAT dysregulation and a secondary inflammatory state contribute to disease pathogenesis and phenotype. JAK-inhibitors abrogate signaling and modulate cytokine excess, leading to symptomatic improvement but have modest impact on overall survival. Additional aspects of disease pathogenesis require urgent investigation of novel therapeutic strategies if significant improvement in survival is to be achieved. Restoring the immune response to cancer has been demonstrated to be clinically successful in refractory solid tumors and lymphoid malignancies. We hypothesize that MF pathogenesis involves evasion of the anti-tumor response. Restoring the immune response to cancer has proven clinically successful in patients with cancer with antagonism of the interaction between PD1 and PDL1 being the most widely investigated and established approach. As an urgently required innovative approach to MF therapy involves the application of anti-PDL1 therapy; we thus propose a 10 patient pilot study to 1) Determine the rate of lymphocyte subset response to anti-PDL1 therapy, 2) Characterize changes in the cytokine milieu 3) Measure changes in soluble PDL1 and bone marrow PDL1 expression 4) Evaluate the safety, tolerability, and efficacy of anti-PDL1 therapy in patients with MF.

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