Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin.

H. Shinohara, D. Fan, S. Ozawa, S. Yano, M. Van Arsdell, J. L. Viner, R. Beers, I. Pastan, I. J. Fidler

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TfR) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TfR and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins.

Original languageEnglish (US)
Pages (from-to)643-651
Number of pages9
JournalInternational journal of oncology
Volume17
Issue number4
StatePublished - Oct 2000

Fingerprint

Immunotoxins
Transferrin Receptors
Colonic Neoplasms
Liver
Neoplasm Metastasis
Exotoxins
Therapeutic Uses
Pseudomonas
Nude Mice
Neoplasms
Flow Cytometry
Colon
Immunohistochemistry
Monoclonal Antibodies
Carbohydrates
Carcinoma
Antigens
Antibodies
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin. / Shinohara, H.; Fan, D.; Ozawa, S.; Yano, S.; Van Arsdell, M.; Viner, J. L.; Beers, R.; Pastan, I.; Fidler, I. J.

In: International journal of oncology, Vol. 17, No. 4, 10.2000, p. 643-651.

Research output: Contribution to journalArticle

Shinohara, H, Fan, D, Ozawa, S, Yano, S, Van Arsdell, M, Viner, JL, Beers, R, Pastan, I & Fidler, IJ 2000, 'Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin.', International journal of oncology, vol. 17, no. 4, pp. 643-651.
Shinohara, H. ; Fan, D. ; Ozawa, S. ; Yano, S. ; Van Arsdell, M. ; Viner, J. L. ; Beers, R. ; Pastan, I. ; Fidler, I. J. / Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin. In: International journal of oncology. 2000 ; Vol. 17, No. 4. pp. 643-651.
@article{1288e1c1c1394ee2b985961fa8c9eea5,
title = "Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin.",
abstract = "We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TfR) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TfR and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins.",
author = "H. Shinohara and D. Fan and S. Ozawa and S. Yano and {Van Arsdell}, M. and Viner, {J. L.} and R. Beers and I. Pastan and Fidler, {I. J.}",
year = "2000",
month = "10",
language = "English (US)",
volume = "17",
pages = "643--651",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "4",

}

TY - JOUR

T1 - Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin.

AU - Shinohara, H.

AU - Fan, D.

AU - Ozawa, S.

AU - Yano, S.

AU - Van Arsdell, M.

AU - Viner, J. L.

AU - Beers, R.

AU - Pastan, I.

AU - Fidler, I. J.

PY - 2000/10

Y1 - 2000/10

N2 - We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TfR) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TfR and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins.

AB - We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TfR) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TfR and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins.

UR - http://www.scopus.com/inward/record.url?scp=0034294790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034294790&partnerID=8YFLogxK

M3 - Article

C2 - 10995873

AN - SCOPUS:0034294790

VL - 17

SP - 643

EP - 651

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 4

ER -