Abstract
Immunotoxins and other antibody-based therapeutic reagents have proved effective against lymphomas and leukemias but results with carcinomas and other solid tumors have thus far proved disappointing. A major reason for this difference is that solid tumors are relatively impermeable to macromolecules. A solution to this problem would be to attack the endothelial cells of the tumor vascular bed rather than the tumor cells themselves. We have developed a mouse model of this 'vascular targeting' approach where genetic modification of the tumor cells causes them to induce the expression of an experimental marker (MHC Class II) on tumor endothelium. In this report we show that an anti-Class II-deglycosylated Ricin A-chain immunotoxin kills activated endothelial cells in tissue culture and, when injected into appropriate tumor-bearing mice, causes complete thrombosis of the tumor vasculature and dramatic regressions of large solid tumors. These findings suggest that therapeutic agents derived from recently-described antibodies against human tumor endothelium could provide a general treatment for disseminated solid cancers in man.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 195-202 |
| Number of pages | 8 |
| Journal | Journal of Controlled Release |
| Volume | 28 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - 1994 |
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Keywords
- Antibody
- Endothelial cell
- Immunotoxin
- Solid tumor
- Therapy
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Targeting the vasculature of solid tumors. / Burrows, F. J.; Thorpe, P. E.
In: Journal of Controlled Release, Vol. 28, No. 1-3, 1994, p. 195-202.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting the vasculature of solid tumors
AU - Burrows, F. J.
AU - Thorpe, P. E.
PY - 1994
Y1 - 1994
N2 - Immunotoxins and other antibody-based therapeutic reagents have proved effective against lymphomas and leukemias but results with carcinomas and other solid tumors have thus far proved disappointing. A major reason for this difference is that solid tumors are relatively impermeable to macromolecules. A solution to this problem would be to attack the endothelial cells of the tumor vascular bed rather than the tumor cells themselves. We have developed a mouse model of this 'vascular targeting' approach where genetic modification of the tumor cells causes them to induce the expression of an experimental marker (MHC Class II) on tumor endothelium. In this report we show that an anti-Class II-deglycosylated Ricin A-chain immunotoxin kills activated endothelial cells in tissue culture and, when injected into appropriate tumor-bearing mice, causes complete thrombosis of the tumor vasculature and dramatic regressions of large solid tumors. These findings suggest that therapeutic agents derived from recently-described antibodies against human tumor endothelium could provide a general treatment for disseminated solid cancers in man.
AB - Immunotoxins and other antibody-based therapeutic reagents have proved effective against lymphomas and leukemias but results with carcinomas and other solid tumors have thus far proved disappointing. A major reason for this difference is that solid tumors are relatively impermeable to macromolecules. A solution to this problem would be to attack the endothelial cells of the tumor vascular bed rather than the tumor cells themselves. We have developed a mouse model of this 'vascular targeting' approach where genetic modification of the tumor cells causes them to induce the expression of an experimental marker (MHC Class II) on tumor endothelium. In this report we show that an anti-Class II-deglycosylated Ricin A-chain immunotoxin kills activated endothelial cells in tissue culture and, when injected into appropriate tumor-bearing mice, causes complete thrombosis of the tumor vasculature and dramatic regressions of large solid tumors. These findings suggest that therapeutic agents derived from recently-described antibodies against human tumor endothelium could provide a general treatment for disseminated solid cancers in man.
KW - Antibody
KW - Endothelial cell
KW - Immunotoxin
KW - Solid tumor
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=0028207108&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028207108&partnerID=8YFLogxK
U2 - 10.1016/0168-3659(94)90166-X
DO - 10.1016/0168-3659(94)90166-X
M3 - Article
AN - SCOPUS:0028207108
VL - 28
SP - 195
EP - 202
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1-3
ER -