Comparative localization of glioma-reactive monoclonal antibodies in vivo in an athymic mouse human glioma xenograft model.

Details

Serval ID
serval:BIB_B34B3C23ECC5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comparative localization of glioma-reactive monoclonal antibodies in vivo in an athymic mouse human glioma xenograft model.
Journal
Journal of Neuroimmunology
Author(s)
Wikstrand C.J., McLendon R.E., Carrel S., Kemshead J.T., Mach J.P., Coakham H.B., de Tribolet N., Bullard D.E., Zalutsky M.R., Bigner D.D.
ISSN
0165-5728 (Print)
ISSN-L
0165-5728
Publication state
Published
Issued date
1987
Volume
15
Number
1
Pages
37-56
Language
english
Abstract
Radioiodinated murine monoclonal antibodies (Mabs) 81C6, Me 1-14, C12, D12, and E9, made against or reactive with human gliomas but not normal brain, and Mab UJ13A, a pan-neuroectodermal Mab reactive with normal human glial and neural cells, were evaluated in paired label studies in the D-54 MG subcutaneous human glioma xenograft model system in nude mice. Following intravenous injection in the tail vein of mice bearing 200-400 mm3 tumors, specific localization of Mabs to tumor over time (6 h-9 days) was evaluated by tissue counting; each Mab demonstrated a unique localization profile. The comparison of localization indices (LI), determined as a ratio of tissue level of Mab to control immunoglobulin with simultaneous correction for blood levels of each, showed Mabs 81C6 and Me 1-14 to steadily accumulate in glioma xenografts, maintaining LI from 5-20 at 7-9 days after Mab injection. Mab UJ13A peaked at day 1, maintaining this level through day 2, and declining thereafter. Mabs D12 and C12 peaked at days 3 and 4, respectively, and E9 maintained an LI of greater than 3 from days 3-9. Percent injected dose localized/g of tumor varied from a peak high of 16% (81C6) to a low of 5% (Me 1-14 and UJ13A). Immunoperoxidase histochemistry, performed with each Mab on a battery of primary human brain neoplasms, revealed that Mabs 81C6 and E9, which demonstrated the highest levels of percent injected dose localized/g of tumor over time, reacted with antigens expressed in the extracellular matrix. This finding suggests that extracellular matrix localization of antigen represents a biologically significant factor affecting localization and/or binding in the xenograft model used. The demonstration of significant localization, varied kinetics and patterns of localization of this localizing Mab panel warrants their continued investigation as potential imaging and therapeutic agents for human trials.
Keywords
Animals, Antibodies, Monoclonal/diagnostic use, Antigen-Antibody Complex/analysis, Antigens, Neoplasm/analysis, Cell Line, Glioma/immunology, Glioma/pathology, Humans, Mice, Mice, Nude, Neoplasm Transplantation, Transplantation, Heterologous
Pubmed
Web of science
Create date
25/04/2013 14:05
Last modification date
20/08/2019 15:21
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