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

被引:32
作者
Baluna, R [1 ]
Vitetta, ES [1 ]
机构
[1] Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA
关键词
immunotoxin; animal models; severe combined immunodeficient mouse;
D O I
10.1097/00002371-199901000-00006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:41 / 47
页数:7
相关论文
共 74 条
[51]   CONTINUOUS-INFUSION OF THE ANTI-CD22 IMMUNOTOXIN IGG-RFB4-SMPT-DGA IN PATIENTS WITH B-CELL LYMPHOMA - A PHASE-I STUDY [J].
SAUSVILLE, EA ;
HEADLEE, D ;
STETLERSTEVENSON, M ;
JAFFE, ES ;
SOLOMON, D ;
FIGG, WD ;
HERDT, J ;
KOPP, WC ;
RAGER, H ;
STEINBERG, SM ;
GHETIE, V ;
SCHINDLER, J ;
UHR, J ;
WITTES, RE ;
VITETTA, ES .
BLOOD, 1995, 85 (12) :3457-3465
[52]  
SCULIER JP, 1988, INTENS CARE MED, V14, P666
[53]   PREVENTION OF IMMUNOTOXIN-MEDIATED VASCULAR LEAK SYNDROME IN RATS WITH RETENTION OF ANTITUMOR-ACTIVITY [J].
SIEGALL, CB ;
LIGGITT, D ;
CHACE, D ;
TEPPER, MA ;
FELL, HP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (20) :9514-9518
[54]  
Soballe PW, 1996, CANCER RES, V56, P757
[55]   THE TOXICITY OF CHEMICALLY DEGLYCOSYLATED RICIN A-CHAIN IN MICE [J].
SOLERRODRIGUEZ, AM ;
UHR, JW ;
RICHARDSON, J ;
VITETTA, ES .
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY, 1992, 14 (02) :281-291
[56]   A PHASE-I TRIAL OF CONTINUOUS-INFUSION INTERLEUKIN-4 (IL-4) ALONE AND FOLLOWING INTERLEUKIN-2 (IL-2) IN CANCER-PATIENTS [J].
SOSMAN, JA ;
FISHER, SG ;
KEFER, C ;
FISHER, RI ;
ELLIS, TM .
ANNALS OF ONCOLOGY, 1994, 5 (05) :447-452
[57]   A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma [J].
Stone, MJ ;
Sausville, EA ;
Fay, JW ;
Headlee, D ;
Collins, RH ;
Figg, WD ;
StetlerStevenson, M ;
Jain, V ;
Jaffe, ES ;
Solomon, D ;
Lush, RM ;
Senderowicz, A ;
Ghetie, V ;
Schindler, J ;
Uhr, JW ;
Vitetta, ES .
BLOOD, 1996, 88 (04) :1188-1197
[58]   CURRENT STATUS OF INTERLEUKIN-2 THERAPY IN CANCER [J].
TARTOUR, E ;
MATHIOT, C ;
FRIDMAN, WH .
BIOMEDICINE & PHARMACOTHERAPY, 1992, 46 (10) :473-484
[59]  
TEELUCKSINGH S, 1990, Q J MED, V75, P515
[60]  
TOM WW, 1983, ARCH SURG-CHICAGO, V118, P636