Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia

Abstract

In addition to chemotherapy and irradiation, in the context of allogeneic stem cell transplantation (SCT), the donor cell-mediated antileukemic effect can lead to sustained complete remissions, also in cases of a large tumor load. This phenomenon appears to be an immunologically mediated response, possibly due to various effector cell populations. Cytotoxic T-lymphocyte (CTL) responses against minor histocompatibility antigens with restricted tissue distribution, in particular restricted to some or all hematopoietic cells, may be highly efficient in inducing anti-leukemic responses for adoptive immunotherapy. Specific CTL responses against leukemia-associated antigens may be generated using leukemic cells modified to coexpress costimulatory molecules identical to professional antigen-presenting cells. Donor-derived T cells recognizing such antigens may be used in the context of allogeneic SCT to induce complete and sustained remissions, also in patients with leukemia refractory to chemotherapy. In these circumstances, the primary objective of allogeneic SCT may be not to diminish the number of malignant cells by the chemotherapy and irradiation as part of the conditioning regimen, but to allow immunotherapy against leukemic cells using donor lymphocyte populations.