Can immune therapy cure acute myeloid leukemia?
There is considerable progress in immune therapy of diverse cancers. In haematology these advances are mostly limited to lymphoid cancers. Effective therapies include monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells to lymphoid lineage-antigens such as CD19, CD20 and B-cell maturation antigen (BCMA). Gemtuzumab ozogamicin (Myelotarg®) is the only FDA-approved immune-based therapy for acute myeloid leukemia (AML). Several clinical trials of antibodies to CD38 and CD123 are reported with unimpressive efficacy and safety concerns. Reasons are higher daily production rates of myeloid cells and unacceptable collateral damage to normal haematopoietic cells because of imperfect specificity for AML cells. Potential targets of anti-AML immune therapy are (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens. Data supporting an effective allogeneic anti-AML effect come from studies in recipients of haematopoietic cell transplants with graft-versus-host disease (GvHD) and recipients of donor lymphocyte infusions (DLI). A special problem is a relative paucity of neo-antigens in AML compared with solid cancers because of a low cumulative mutation frequency. Cell immune therapy trials are in progress including CAR-T-cells, CAR-NK-cells and allogeneic NK-cells. Approaches using synthetic biology are being developed. Presently, except for gemtuzumab ozogamicin there are no convincing data of efficacy of immune therapy in AML.