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Based on progress to date, Dr. Bonifant was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. There is a clear need for new treatment options for pediatric relapsed or refractory acute leukemia. Patients receiving standard chemotherapy regimens continue to suffer a poor prognosis. Immunotherapy has the potential to fulfill this need through its precise tumor targeting and novel anticancer biology. Recently, a type of immune cell, the T cell, has been genetically modified to specifically recognize leukemia cells through a specialized receptor (CAR). Infusion of CAR-T cells has shown stunning anti-leukemia activity in clinical trials. However, this approach has key limitations. Importantly, CAR-T cell persistence in each patient is critical to ensure continued disease remission. Alterations in leukemia surface protein expression have also been reported as a mode of CAR-T evasion. These may lead to disease relapse. Dr. Bonifant and her colleagues believe they can introduce new elements to existing chimeric receptors to promote improved CAR-T survival. They also believe they can alter these cells to target more than one surface antigen -- to prevent antigen loss and CAR-T escape, while enhancing specific disease targeting. The overall rationale for this proposal is the confidence in CAR-T cells as a powerful addition to anti-leukemia therapy. Dr. Bonifant would like to facilitate continued improvement of this therapeutic modality in order to ultimately attain durable cures.

The 2021, 2022, and 2023 portions of this grant are funded by and named for Emily Beazley's Kures for Kids Fund, a St. Baldrick's Hero Fund. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.

The 2020 portion of this grant is funded by and named for the Rally for Ryan Fund, a St. Baldrick's Hero Fund. Ryan was diagnosed with high risk ALL when he was seven years old. He endured 3 ½ years of often harsh treatments with smiles, laughter and a brave acceptance that this was his fight to win. And Ryan did prevail—he took his last chemo pill in January 2016 but relapsed at the end of the year. He endured CAR T-cell therapy and a bone marrow transplant and is once again cancer-free. This fund honors Ryan’s commitment to help make a difference for kids with cancer.