[Antibody-Drug Conjugate for Treating Leukemia and Lymphoma-The Present Status, Problems, and Future Development]

Antibody-drug conjugate(ADC)contain monoclonal antibodies that target-specific tumor antigens, cytotoxic payloads, and linkers. ADCs use antibodies to selectively act on tumors, making them more effective and less toxic. In Japan, 4 drugs are approved as ADCs for leukemia and lymphoma: gemtuzumab ozogamicin(GO)consists of an anti-CD33 monoclonal antibody bound to calicheamicin via a linker, approved for relapsed/refractory acute myeloid leukemia. Brentuximab vedotin (BV)has anti-CD30 antibodies bound to MMAE via a linker and is approved for CD30-positive Hodgkin's lymphoma, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma. BV, in combination with multi-agent chemotherapy, resulted in significantly prolonged progression-free survival(PFS)in classical Hodgkin's lymphoma and peripheral T-cell lymphoma compared to the control group. Inotuzumab ozogamicin(IO)has an anti-CD22 antibody bound to calicheamicin via a linker, approved for relapsed/refractory CD22-positive B-cell acute lymphoblastic leukemia. In relapsed/refractory B-cell acute lymphoblastic leukemia, IO showed a higher complete remission rate than the control group. Polatuzumab vedotin(PV)has an anti-CD79b monoclonal antibody bounds to MMAE via a linker, approved for diffuse large B-cell lymphoma(DLBCL). In DLBCL patients with an international prognostic index score(IPI score)of 2 or higher, the combination of PV plus rituximab, cyclophosphamide, doxorubicin, and prednisone(PV+R-CHP)extended PFS at 2 years compared with R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), which has long been the standard of care. As shown, ADCs exhibit high therapeutic efficacy in leukemia and lymphoma treatment, but many aspects of their resistance mechanisms remain unclear and require further research.