Clinical Experience with Bispecific T Cell Engagers

Bispecific T cell engagers are antibody constructs directed to a tumor-specific target on the one hand and to CD3-positive T cells on the other hand. Blinatumomab is a compound with specificity for the pan-B cell marker CD19. Clinical activity was tested in relapsed and refractory (R/R) non-Hodgkin's Lymphoma (NHL), R/R acute lymphoblastic leukemia (ALL), and ALL patients with minimal residual disease. Trials have already been started in de novo ALL. The most clinically relevant toxicities are neurologic events and cytokine release syndrome as with other T cell-activating therapies. The mechanisms of resistance are not fully understood. Higher leukemia load and later stage disease represent unfavorable factors. Besides, an upregulation of regulatory T cells and inhibitory molecules like PD-1/PD-L1 may have a role as the loss of target by several mechanisms. The future will show whether the use of bispecifics in ALL can change the standard treatment algorithms and whether bispecific T cell engagers will also be successfully used in other malignant entities.