Allogeneic transplantation as anticancer immunotherapy

• Allogeneic immunity can cure cancers resistant to standard chemotherapy.
• The main barrier to allogeneic immunotherapy is graft versus host disease (GVHD).
• Allogeneic NK cells can limit GVHD by eliminating host antigen presenting cells.
• Allogeneic transplant principles can be applied to other adoptive immunotherapies.

Allogeneic stem cell transplantation (AlloSCT) utilizes HLA-matched donor bone marrow or peripheral blood stem cell grafts to reconstitute haematopoiesis and immunity in patients with bone marrow failure or hematological malignancies. It is now clear that much of the anti-cancer effect of AlloSCT is due to the ability of engrafting donor derived lymphocyte populations to eradicate residual malignant clones, through a phenomenon known as the graft-versus-tumor (GVT) effect. Recognition of the importance of GVT in the long-term control of cancer has allowed substantial reductions in the pre-transplant conditioning intensity, leading to the development of reduced-intensity or even non-myeloablative transplant regimens in some patient groups. These reduced intensity regimens still allow donor cell engraftment and GVT, whilst reducing the morbidity and mortality associated with traditional myeloablative conditioning. Through clinical observations and experimental models of AlloSCT substantial insights have been provided into the mechanisms of immunological control of malignancy even outside the setting of AlloSCT, providing an opportunity to duplicate these anti-cancer mechanisms via non-allogeneic immunotherapies.