Localization of an antibody to CD74 (MHC class II invariant chain) to human B cell lymphoma xenografts in nude mice |
| |
Authors: | Lisa Shih Gaik Lin Ong Jack Burton Dina Mishina David M Goldenberg M Jules Mattes |
| |
Institution: | (1) Garden State Cancer Center, 520 Belleville Avenue, Belleville, NJ, 07109, USA e-mail: mjmattes.gscancer@worldnet.att.net Tel.: +1-973-844-7013 Fax: +1-973-844-7020, US |
| |
Abstract: | The tumor-specific localization of an anti-CD74 Ab, LL1, was demonstrated in nude mice bearing xenografts of human B-cell
lymphoma. This Ab, conjugated to radionuclides emitting Auger electrons, including 125I and 111In, was previously reported to kill tumor cells in vitro effectively and specifically. The cytotoxic potency of this Ab is
due to its uptake and catabolism at a very high level, which also affected the Ab biodistribution experiments. Thus, Ab localization
to the tumor was only detected if a “residualizing” radiolabel was used, meaning a label that is trapped within cells, usually
within lysosomes, after catabolism of the Ab to which it was conjugated. Similar results were obtained with three different
residualizing labels: 111In conjugated via the chelators benzyl diethylenetriaminepentaacetic acid (DTPA) or 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic
acid (DOTA), or 131I-dilactitol-tyramine, a residualizing form of iodine. The Ab protein dose could be high, 0.5 mg/mouse, without causing a
decrease in specific tumor uptake, probably reflecting the high capacity for uptake. Moreover, tumors of moderate size were
found to cause rapid, specific removal of the Ab from the blood, also a result of catabolic processes. This induced blood
clearance naturally affected the Ab localization experiments, but this factor could be circumvented by increasing the Ab protein
dose. Using a different Ab, anti-(mature MHC class II), the ability of Ab to penetrate relatively large solid tumors was investigated.
Complete saturation of antigenic sites was observed in tumors up to 0.3 g in size, but quite high Ab protein doses were required,
5.0 mg/mouse. These results provide a rationale for attempting therapy with radiolabeled LL1.
Received: 4 November 1999 / Accepted: 19 January 2000 |
| |
Keywords: | CD74 Radiolabeled Ab Radioimmunotherapy B cell lymphoma Major histocompatibility complex class II invariant chain |
本文献已被 PubMed SpringerLink 等数据库收录! |
|