Falkenburg J H, Smit W M, Willemze R
Department of Hematology, Leiden University Medical Center, The Netherlands.
Immunol Rev. 1997 Jun;157:223-30. doi: 10.1111/j.1600-065x.1997.tb00985.x.
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.
除化疗和放疗外，在异基因干细胞移植（SCT）的情况下，供体细胞介导的抗白血病效应可导致持续完全缓解，即使在肿瘤负荷较大的情况下也是如此。这种现象似乎是一种免疫介导的反应，可能是由于各种效应细胞群体所致。针对组织分布受限的次要组织相容性抗原的细胞毒性T淋巴细胞（CTL）反应，特别是仅限于部分或所有造血细胞的反应，在诱导过继性免疫治疗的抗白血病反应中可能非常有效。使用经过修饰以共表达与专职抗原呈递细胞相同的共刺激分子的白血病细胞，可以产生针对白血病相关抗原的特异性CTL反应。识别此类抗原的供体来源的T细胞可用于异基因SCT，以诱导完全和持续缓解，即使在对化疗难治的白血病患者中也是如此。在这些情况下，异基因SCT的主要目标可能不是通过作为预处理方案一部分的化疗和放疗来减少恶性细胞的数量，而是允许使用供体淋巴细胞群体对白血病细胞进行免疫治疗。
