Therapeutic effect of novel anti-human Fas antibody HFE7A on graft-versus-host disease model

In order to evaluate anti-human Fas antibody, we have established a new gra ft-versus-host disease (GVHD) model wherein splenocytes of human Fas transg enic mice (hFas-TgM) were transferred to immune-deficient SCID mice. In thi s model, although host SCLD cells are not activated by or responsive to gra ft hFas-TgM cells, graft hFas-TgM cells are activated by and responsive to host SCID cells and thus cause GVHD symptoms. SCID mice that received hFas- TgM splenocytes had increased human Fas-positive lymphocytes in lymph nodes , decreased in body weight, and developed skin diseases, including rash and alopecia, Administration of novel anti-human Fas antibody HFE7A, which did not induce liver toxicity after administration to mice, decreased the leve l of the human Fas-positive lymphocytes, blocked the decrease of body weigh t, and suppressed development of skin diseases in this model. These results indicate that induction of apoptosis to activated graft cells with nontoxi c anti-Fas antibody could reduce GVHD symptoms. (C) 2001 Academic Press.