TY - JOUR
T1 - An in vivo model to study immunotoxin-induced vascular leak in human tissue
AU - Baluna, Roxana
AU - Vitetta, Ellen S.
PY - 1999
Y1 - 1999
N2 - Phase I/II clinical trials using ricin A chain-containing immunotoxins (RTA-ITs) in >125 patients with lymphoma have established that vascular leak syndrome (VLS) is the dose-limiting toxicity. A similar side effect has also been described for other immunotoxins (ITs) and for cytokines, growth factors, antibodies, and chemotherapeutic agents. To better reproduce the conditions underlying vascular leak syndrome in patients treated with immunotoxins, human skin grafts were transplanted onto SCID mice and modifications in the graft were studied after systemic administration of a RTA-IT. Compared with mice receiving saline, an increase in wet/dry weight ratios of these grafts was observed in mice injected with RTA-IT. An increase in the permeability of the human blood vessels was also demonstrated by the extravasation of Carbon Black and the accumulation of Evans Blue dye in the graft. Taken together, these observations suggest that the RTA-IT can induce VLS-like manifestations. This model should facilitate the testing of potential inhibitors of VLS, which might reduce the toxicity of ITs and other therapeutic agents.
AB - Phase I/II clinical trials using ricin A chain-containing immunotoxins (RTA-ITs) in >125 patients with lymphoma have established that vascular leak syndrome (VLS) is the dose-limiting toxicity. A similar side effect has also been described for other immunotoxins (ITs) and for cytokines, growth factors, antibodies, and chemotherapeutic agents. To better reproduce the conditions underlying vascular leak syndrome in patients treated with immunotoxins, human skin grafts were transplanted onto SCID mice and modifications in the graft were studied after systemic administration of a RTA-IT. Compared with mice receiving saline, an increase in wet/dry weight ratios of these grafts was observed in mice injected with RTA-IT. An increase in the permeability of the human blood vessels was also demonstrated by the extravasation of Carbon Black and the accumulation of Evans Blue dye in the graft. Taken together, these observations suggest that the RTA-IT can induce VLS-like manifestations. This model should facilitate the testing of potential inhibitors of VLS, which might reduce the toxicity of ITs and other therapeutic agents.
KW - Animal models
KW - Immunotoxin
KW - Severe combined immunodeficient mouse
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U2 - 10.1097/00002371-199901000-00006
DO - 10.1097/00002371-199901000-00006
M3 - Article
C2 - 9924698
AN - SCOPUS:0032943931
SN - 1053-8550
VL - 22
SP - 41
EP - 47
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 1
ER -