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 graft-versus-host disease (GVHD) model wherein splenocytes of human Fas transgenic mice (hFas-TgM) were transferred to immune-deficient SCID mice. In this model, although host SCID cells are not activated by or responsive to graft 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 level of the human Fas-positive lymphocytes, blocked the decrease of body weight, and suppressed development of skin diseases in this model. These results indicate that induction of apoptosis to activated graft cells with nontoxic anti-Fas antibody could reduce GVHD symptoms.
Kuwahara
H
H
Neuroscience and Immunology Research Laboratories, Sankyo Co., Ltd., Tokyo, 140-8710, Japan.
Tani
Y
Y
Ogawa
Y
Y
Takaichi
Y
Y
Shiraishi
A
A
Ohtsuki
M
M
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D019014:fas Receptor