Endoglin CAR T cells for Immunotherapy of Ewing Sarcoma
Ewing sarcoma is the second common bone cancer in children and young adults. It is an aggressive type of cancer that spreads rapidly to other organs in the body. Ewing sarcoma that recurs or that has spread to other parts of the body often fails standard treatment and is fatal. An alternative approach using genetically engineered T cells can potentially address this treatment failure. T cells modified to express an artificial molecule named chimeric antigen receptor (CAR) can redirect the T cells to cancer sites and specifically kill cancer cells. CAR T cells have proved transformational in treating leukemia, a common blood cancer. We have developed a novel CAR molecule that targets a protein called endoglin present on aggressive forms of Ewing sarcoma. Endoglin was identified as a target of body’s own immune response leading to cancer remission in a child with advanced sarcoma in our clinical trial. The CAR T cells specific to endoglin can travel to multiple sites in the body and kill the cancer cells expressing endoglin. We also propose to combine immune checkpoint inhibitors (ICIs), along with endoglin-specific CAR T cells. These are antibodies that help to take the brakes off of the immune system by blocking immune response dampers. ICIs will unleash the ability endoglin CAR T cells to completely and irreversibly eradicate resistant Ewing sarcoma. In this project, we will i) test the function of endoglin-targeting CAR T cells against experimental Ewing sarcoma and ii) assess the combination of endoglin CAR T cells with ICIs for treating this hard-to-cure cancer. Once successfully developed, endoglin CAR T cells along with ICIs can be readily translated to the clinic to benefit patients with advanced Ewing sarcoma.