CD123-Engager T Cells As a Novel Immunotherapeutic for AML

Background:The outcome for patients with high risk acute myeloid leukemia (AML) remains poor. Thus new targeted therapies are needed and immunotherapies have the potential to fulfill this need. Adoptive transfer of tumor-specific T cells is one promising approach; however infused T cells do not redirect the large reservoir of resident T cells to tumors. To overcome this limitation we have recently developed a new approach to render T cells specific for tumor cells, which relies on genetically modifying T cells with a secretable, bispecific T cell engager (ENG-T cells). Secretion of bispecific protein should activate infused cells as well as bystander T cells against tumor. Consistent and prolonged synthesis of engagers by T cells should be superior to the intermittent, direct infusion of the recombinant bispecific antibody, not only because these recombinant proteins have short half-lives but also because they do not accumulate at tumor sites. The goal of this project was to generate T cells secreting IL3Rα (CD123) and CD3 bispecific T cell engagers (CD123-ENG T cells) and to evaluate their effector function in vitroand in vivo.