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Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts.

Publication ,  Journal Article
Colapinto, EV; Humphrey, PA; Zalutsky, MR; Groothuis, DR; Friedman, HS; de Tribolet, N; Carrel, S; Bigner, DD
Published in: Cancer Res
October 15, 1988

Monoclonal antibodies (MAbs) targeted to glioma-associated antigens may allow the selective delivery of imaging and therapeutic agents to brain tumors; the use of MAb fragments may be a strategy to further improve tumor uptake of such agents relative to normal tissues. In this study, we have examined the in vivo localization of radioiodinated MAb Me1-14, a murine immunoglobulin G2a (IgG2a) reactive with gliomas, and its F(ab')2 fragment in s.c. and intracranial xenografts of human glioma cell line D-54 MG in athymic mice. The radiolabeled F(ab')2 fragment of Me1-14 was demonstrated to possess in vitro binding affinity and immunoreactivity comparable to that of whole IgG. Direct comparison of IgG and F(ab')2 biodistribution in s.c. xenograft-bearing mice showed higher tumor: normal tissue ratios of the F(ab')2 fragment compared to IgG. In intracranial tumor-bearing mice paired-label analysis using a nonspecific protein control showed earlier specific tumor localization by the F(ab')2 fragment of Me1-14 compared to IgG. Blood-to-tumor transfer constants (K1) derived for Me1-14 F(ab')2 were significantly greater than those for whole Me1-14 (P = 0.01). Estimated radiation dosimetry revealed that 131I-labeled Me1-14 F(ab')2 would deliver higher radiation doses to tumor than to normal tissues. These studies demonstrate that the F(ab')2 fragment of Me1-14 may be a potential agent for immune-directed brain tumor diagnosis and therapy.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 15, 1988

Volume

48

Issue

20

Start / End Page

5701 / 5707

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Immunoglobulin G
  • Immunoglobulin Fab Fragments
  • Humans
  • Glioma
  • Cell Line
  • Antibodies, Monoclonal
 

Citation

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Colapinto, E. V., Humphrey, P. A., Zalutsky, M. R., Groothuis, D. R., Friedman, H. S., de Tribolet, N., … Bigner, D. D. (1988). Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts. Cancer Res, 48(20), 5701–5707.
Colapinto, E. V., P. A. Humphrey, M. R. Zalutsky, D. R. Groothuis, H. S. Friedman, N. de Tribolet, S. Carrel, and D. D. Bigner. “Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts.Cancer Res 48, no. 20 (October 15, 1988): 5701–7.
Colapinto EV, Humphrey PA, Zalutsky MR, Groothuis DR, Friedman HS, de Tribolet N, et al. Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts. Cancer Res. 1988 Oct 15;48(20):5701–7.
Colapinto, E. V., et al. “Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts.Cancer Res, vol. 48, no. 20, Oct. 1988, pp. 5701–07.
Colapinto EV, Humphrey PA, Zalutsky MR, Groothuis DR, Friedman HS, de Tribolet N, Carrel S, Bigner DD. Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts. Cancer Res. 1988 Oct 15;48(20):5701–5707.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 15, 1988

Volume

48

Issue

20

Start / End Page

5701 / 5707

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Immunoglobulin G
  • Immunoglobulin Fab Fragments
  • Humans
  • Glioma
  • Cell Line
  • Antibodies, Monoclonal