The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice

Tadahiro Matsudaira, Hideki Kodo, Shin Ichiro Okamoto, Kenzaburo Tani, Arinobu Tojo, Keiya Ozawa, Kiro Asano, Shigetaka Asano

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5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)676-681
Number of pages6
JournalTransplantation
Volume54
Issue number4
Publication statusPublished - 1992 Oct

ASJC Scopus subject areas

  • Transplantation

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