An in vivo model to study immunotoxin-induced vascular leak in human tissue

Roxana Baluna, Ellen S. Vitetta

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)41-47
Number of pages7
JournalJournal of Immunotherapy
Volume22
Issue number1
DOIs
StatePublished - 1999

Fingerprint

Immunotoxins
Blood Vessels
Transplants
Soot
Ricin
Evans Blue
Phase II Clinical Trials
Clinical Trials, Phase I
SCID Mice
Permeability
Lymphoma
Intercellular Signaling Peptides and Proteins
Coloring Agents
Cytokines
Weights and Measures
Skin
Antibodies

Keywords

  • Animal models
  • Immunotoxin
  • Severe combined immunodeficient mouse

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

An in vivo model to study immunotoxin-induced vascular leak in human tissue. / Baluna, Roxana; Vitetta, Ellen S.

In: Journal of Immunotherapy, Vol. 22, No. 1, 1999, p. 41-47.

Research output: Contribution to journalArticle

@article{38c426e0ecfb4ab492e917f456f7609b,
title = "An in vivo model to study immunotoxin-induced vascular leak in human tissue",
abstract = "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.",
keywords = "Animal models, Immunotoxin, Severe combined immunodeficient mouse",
author = "Roxana Baluna and Vitetta, {Ellen S.}",
year = "1999",
doi = "10.1097/00002371-199901000-00006",
language = "English (US)",
volume = "22",
pages = "41--47",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=0032943931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032943931&partnerID=8YFLogxK

U2 - 10.1097/00002371-199901000-00006

DO - 10.1097/00002371-199901000-00006

M3 - Article

C2 - 9924698

AN - SCOPUS:0032943931

VL - 22

SP - 41

EP - 47

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 1

ER -