CYTOTOXIC T-LYMPHOCYTE (CTL) RESPONSES AGAINST ACUTE OR CHRONIC MYELOID-LEUKEMIA

In addition to chemotherapy and irradiation, in the contest of allogen eic stem cell transplantation (SCT), the donor cell-mediated antileuke mic 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 histocompatibilit y antigens with restricted tissue distribution, in particular restrict ed to some or all hematopoietic cells, may be highly efficient in indu cing anti-leukemic responses for adoptive immunotherapy Specific CTL r esponses against leukemia-associated antigens may be generated using l eukemic cells modified to coexpress costimulatory molecules identical to professional antigen-presenting cells. Donor-derived T cells recogn izing such antigens may be used in the context of allogeneic SCT to in duce complete and sustained remissions, also in patients with leukemia refractory to chemotherapy. In these circumstances, the primary objec tive of allogeneic SCT may be not to diminish the number of malignant cells by the chemotherapy and irradiation as part of the conditioning regimen, bur to allow immunotherapy against leukemic cells using donor lymphocyte populations.