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ANTIBODY DELIVERED LYMPHOHEMATOPOIETIC IRRADIATION

抗体递送的淋巴造血辐射

基本信息

批准号：
2084296
负责人：
DANA C MATTHEWS
金额：
$ 7.72万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-01 至 1995-08-31
项目状态：
已结题

项目摘要

We have demonstrated that radiolabeled monoclonal antibodies reactive with the panhematopoietic CD45 antigen can deliver relatively specific irradiation to lymphohematopoietic tissues in preclinical studies in mice and macaques as well as in patients undergoing bone marrow transplantation for acute leukemia. The proposed studies examine strategies for improving the "therapeutic ratio" of radiation delivered to target lymphohematopoietic tissues, as compared to other normal organs, by 131I-labeled anti- CD45 antibody. These will include study of the effect of the use of an unlabeled preclearing dose" of antibody prior to administration of radiolabeled antibody, further definition of the relationship between antibody dose and relative lymphohematopoietic radiation, and the use of isotopes (186Re and 188Re) which have half lives which are shorter than that of 131I. Further studies will determine if radiolabeled anti-CD45 antibody can facilitate the engraftment of donor marrow, alone or with supplemental total body irradiation (TBI), by ablating host marrow and producing immunosuppression in mice undergoing marrow transplantation with T cell-depleted marrow from donors matched or mismatched for minor or major histocompatibility antigens. The ability to increase the dose of radiation to lymphohematopoietic tissues while minimizing the exposure of normal organs may decrease the high rate of relapse in patients undergoing marrow transplantation for advanced leukemia. It may also decrease the high rate of rejection of HLA- mismatched or unrelated donor marrow which has been depleted of T cells in an attempt to lower the incidence of Graft-vs.-Host Disease.

我们已经证明了放射性标记的单抗反应与全血细胞CD45抗原可传递淋巴造血组织的相对特异性照射在小鼠和猕猴以及病人身上进行的临床前研究接受骨髓移植治疗急性白血病。这个拟议的研究审查了改善“治疗性”的策略辐射对靶淋巴造血者的比率组织，与其他正常器官相比，通过131I标记的反义 CD45抗体。这些将包括对使用效果的研究未标记的抗体预清除剂量“之前放射性标记抗体的给药，进一步定义抗体剂量与相对淋巴造血率的关系辐射和同位素(186Re和188Re)的使用比~(131)I的半衰期短。进一步研究将确定放射性标记的抗CD45抗体是否可以促进移植供者骨髓，单独移植或补充全骨髓移植全身照射(TBI)，通过消融宿主骨髓并产生 T细胞骨髓移植小鼠的免疫抑制作用来自相合或不相合的捐赠者的去细胞骨髓主要组织相容性抗原。能够提高最小化淋巴造血组织的辐射剂量暴露正常器官可能会降低高复发率在接受骨髓移植的晚期患者中白血病。还可降低高排斥反应的发生率。不匹配或不相关的供者骨髓已耗尽T细胞细胞，试图降低移植物对宿主的发生率疾病。