CLL-1 CAR-T cells with or without trametinib for the treatment of JMML
JMML is a blood cancer that typically affects infants and toddlers. Many of these children are diagnosed with their leukemia within months of being born. While a child diagnosed today with a more common type of leukemia called “ALL” has an approximately 90% chance of being cured, only 50% of JMML patients are cured with currently available therapies. In addition, JMML patients are only potentially curable if they undergo an intensive treatment called stem cell transplantation which has many side effects. Shockingly, there are zero medications that are FDA approved for the treatment of relapsed JMML. Doctors like myself are left using medications intended for other leukemias and repurposing them for JMML. We will develop a new therapy specifically for JMML called CAR-T cells that works very differently than regular chemotherapy. CAR-T treatments have had miraculous effects in the more common “ALL” type of leukemia, but it has never been tried in JMML patients. CAR-T cells use a patient's own immune system to attack and get rid of the cancer cells. With funds from this ALSF "R Accelerated Award" we will test CAR-T cells in a mouse model of JMML. We will also test the CAR-T cells in combination with an oral medication called trametinib that we recently demonstrated is effective in relapsed JMML. We are hopeful that CAR-T treatments will become available for patients with JMML in the near future based on this work.
Project Goals:
The short-term goal of this project is testing of CAR-T cells, a revolutionary new treatment, in mice that have developed JMML. This would provide the rationale to develop a clinical-grade CAR-T cell product that would be first tested in relapsed JMML patients. The long-term goal of this project is to develop a platform to identify targets for CAR-T cell therapy that could be expanded to other rare blood diseases in which CAR-T cells are not available. For example, patients with pediatric myelodysplastic syndrome or down syndrome associated leukemia would benefit from the development of CAR-T based approaches for patients that don't respond to conventional treatment. In summary, the experiments laid out in this grant are intended to improve outcomes for patients with relapsed JMML and set a precedent for carrying out similar approaches to improve outcomes for other patients with rare but aggressive blood cancers that would benefit from using a patient's immune system to treat cancer.
