Targeting of cytotoxic T cells against leukemic B cells by bispecific antibody (aCD3 x aCD19) does not distract the T cell from its primary target.

Abstract

Bispecific Abs (BsAb) represent a novel format of immunotherapy, recognizing immune effector cells (e.g., T cells), on the one hand, and target cells (e.g., tumor cells), on the other hand. To be successful, cross-linking of the two cell types is necessary for effector cell activation and subsequent killing of the malignant target cells. We asked the question, whether CTL that were incubated with the BsAb aCD3 x aCD19 and malignant B cells and activated to kill the malignant B cells were still able to eliminate their natural target cells (e.g., virus-infected autologous body cells). To test this, HLA-A*0201-restricted, influenza-specific CTL were incubated with BsAb- and HLA-A*0201-positive B lymphoid tumor cells in combination with HLA-A*0201-positive, virus-infected non-B lymphoid cells as natural target cells. The results showed that even in the presence of BsAb and high amounts of tumor B cells, CTL were still capable of eliminating the virus-infected non-B lymphoid target cells; actually, CTL recognized and eliminated the homologous original target cells preferentially.