Antigen-specific allogeneic immunotherapy--selective augmentation of GVL effects

Advancement of chemotherapeutic agents and introduction of molecular-targeted therapy have been improving the prognosis of malignant tumors. However, allogeneic hematopoietic cell transplantation (allo-HCT) still remains the sole curative therapy against chemotherapy-resistant hematological malignancies. Once it was found that full engraftment of donor's immune cells could bring sufficient graft-versus-leukemia/lymphoma(GVL)effects, reduced intensity preconditioning regimens that focus only on suppression of the recipient's immune system so as to allow donor graft engraftment have been introduced into clinics. This has expanded the number of patients eligible for allo-HCT, including elderly patients. Nevertheless, overall survival of patients with high-risk malignancies has not been sufficiently improved. Simple enhancement of donor-derived immunity would result in the increased risk of graft-versus-host disease (GVHD). Here, current and future strategies to selectively enhance GVL effects without inducing detrimental GVHD will be discussed in parallel with their background information and basic concepts.