Optimizing Bispecific Antibody Therapy for Acute Leukemias

Background:

Acute leukemias are blood cancers from which many children and adults will eventually die despite aggressive therapies. There is thus a critical need for new drugs for these tumors. For more than 30 years, proteins (so-called "antibodies") that recognize tumor cells have been envisioned as “magic bullets” for cancer patients but so far have been largely ineffective in acute leukemias. One strategy to render antibodies more active is to modify them so that they recognize leukemia cells and, simultaneously, normal immune cells (typically T-cell lymphocytes), which then selectively kill the attached cancer cell.

Project Goal:

Promising results with one "bispecific" antibody, blinatumomab, were recently reported in some patients with acute leukemia who previously failed intensive chemotherapy. However, because of their small size, these antibodies are quickly eliminated by the kidneys and need to be given via infusion pump over several weeks. Also, for unknown reasons, about half of the patients still do not benefit from these antibodies. Recognizing these limitations, our goal is to develop novel, highly active bispecific antibodies that have longer half-lives and can be given in a simple and safe fashion in the clinic. Through studying how exactly these bispecific antibodies kill leukemia cells, we will not only better understand which patients are most appropriate for these agents but also be able to develop combination treatments that may overcome resistance so that more patients can benefit from them. Together, by optimizing bispecific antibodies, our investigations have the potential to significantly improve the treatment options and outcomes for patients with acute leukemia.