GRAFT VERSUS LEUKEMIA IMMUNOTHERAPY

异基因骨髓移植是一种高效的治疗方法 治疗几种形式的白血病，特别是急性白血病的方法 髓系白血病(AML)和慢性粒细胞白血病(CML)。两个人 移植成功的最大风险因素是发生 移植物抗宿主病(GVHD)或白血病复发， 前者的发病率反过来影响后者的发病率。 从理论上讲，这是因为骨髓接种中的捐赠者T细胞 对移植物抗宿主病负责的基因是针对受体组织相容性抗原的 这也可能存在于残留的白血病细胞上，从而减少 复发的风险。然而，由于GVHD也对 对于接受者来说，根本的问题是GVHD反应性T细胞是否可以 从接种中选择性地消耗，同时保留移植物抗- 白血病(GVL)潜能。为了调查这个问题，我们有 建立实验性异基因小鼠骨髓移植模型 供体/受体株MHC相容，但GVHD相容的模型 针对多种次要组织相容性抗原进行诱导。挑战 具有致死剂量的髓系白血病的受者的情况允许我们评估 可能的免疫治疗抵抗所需的成分 白血病，以及如何最好地做到这一点，同时避免 GVHD。为了实现这一总目标，我们将特别集中我们的 1)同基因B6-GVL活性的免疫学基础 ~gt；B6辐射骨髓移植模型及其对c-myc的挑战 转化的髓系白血病细胞；2)移植物抗白血病的免疫学基础 次要H抗原同种异体C3H.SW-&GT；B6照射骨髓的活性 C-myc转化髓系白血病的挑战移植模型 细胞。

Allogeneic bone marrow transplantation is a highly effective therapeutic approach to curing several forms of leukemia, particularly acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML). The two largest risk factors involved in a successful transplant are the occurrence of either graft-versus-host disease (GVHD) or leukemic relapse, with the incidence of the former inversely affecting the incidence of the latter. Theoretically, this occurs because the donor T cells in the marrow inoculum responsible for GVHD are directed to recipient histocompatibility antigens that may also be present on residual leukemia cells and thereby reduces the risk of relapse. However, since GVHD is also quite devastating to the recipient, the essential question becomes whether GVHD-reactive T cells can be selectively depleted rom an inoculum, while preserving graft-versus- leukemia (GVL) potential. To investigate this question, we have established an experimental allogeneic bone marrow transplantation murine model in which the donor/recipient strains are MHC-compatible, but GVHD can be induced against multiple minor histocompatibility antigens. Challenge of recipients with a lethal dose of myeloid leukemia allows us to assess the components required for possible immunotherapeutic resistance to the leukemia, as well as how this might best be accomplished while avoiding GVHD. To approach this general goal, we specifically will concentrate our efforts on: 1) the immunological basis for GVL activity in a syngeneic B6- >B6 irradiated bone marrow transplantation model with challenge of c-myc transformed myeloid leukemia cells; and 2) the immunological basis for GVL activity in a minor H antigen allogeneic C3H.SW->B6 irradiated bone marrow transplantation model with challenge of c-myc transformed myeloid leukemia cells.