THE ALLOANTIGEN-SPECIFIC IMMUNOSUPPRESSIVE ACTIVITY OF ESTRADIOL-CHLORAMBUCIL CONJUGATE (KM2210) AND ITS BENEFICIAL EFFECT ON ALLOGENEIC BONE-MARROW TRANSPLANTATION IN MICE

被引：6

作者：

MATSUDAIRA, T ^{[1
]}

KODO, H ^{[1
]}

OKAMOTO, SI ^{[1
]}

TANI, K ^{[1
]}

TOJO, A ^{[1
]}

OZAWA, K ^{[1
]}

ASANO, K ^{[1
]}

ASANO, S ^{[1
]}

机构：

[1] METROPOLITAN FUCHU HOSP,DEPT TRANSFUS MED,TOKYO 183,JAPAN

来源：

TRANSPLANTATION | 1992年 / 54卷 / 04期

关键词：

D O I：

10.1097/00007890-199210000-00022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.

引用

页码：676 / 681

页数：6