[Recent progress of bispecific antibody-based therapy for hematological malignancies]

Based on the progress of gene-modification technologies, bispecific antibodies that possess antigen-binding sites with two different specificities have been developed. After the success of blinatumomab for treating refractory B-cell leukemia, series of clinical trials using bispecific antibodies for relapsed and refractory hematological malignancies are being conducted. Several bispecific antibodies target an antigen expressed by tumor cells and the CD3 molecule where binding of bispecific antibodies can generate artificial immunological synapses between tumor cells and human T cells. Therefore, fine tuning of binding affinity and/or structural conformation concomitant with bispecific antibodies may be required to induce antitumor effects and regulate immune-related adverse events, such as cytokine release syndrome. In the future, combination therapy of conventional chemotherapy and/or allogeneic stem-cell transplantation with bispecific antibody therapy will be necessary. Furthermore, molecular target therapy with bispecific antibody therapy is expected to pave the way for next-generation target therapy, resulting in the development of a further effective and safe treatment strategy for hematological malignancies.