Diagnostic and therapeutic evaluation of an anti-langerhans cell histiocytosis monoclonal antibody (NA1/34) in a new Xenograft model
In: International Workshop on Langerhans CellsJournal of investigative dermatology 114(1):127-134; Jg. 114 (2000) 1, S. 127-134
Online
Konferenz
- print, 42 ref
Zugriff:
Scintigraphy using monoclonal antibodies has been suggested as a possible adjunct to conventional staging techniques for the routine staging and diagnosis of Langerhans cell histiocytosis. In this study we have developed a model for Langerhans cell histiocytosis comprising a CD1a-positive subcutaneous xenograft in the flanks of nude (nu/nu) mice. The anti-CD1a murine monoclonal antibody NA1/ 34 was investigated for its potential both as an imaging and as a therapeutic targeting agent in this model. Biodistribution with NA1/34 compared with irrelevant isotype-matched monoclonal antibody demonstrated specific accumulation within the xenografts of 10.0%id per g (percentage injected dose per gram) and 3.3%id per g at 48 h postinjection, respectively. NA1/34 displayed no specific accumulation to CDla-negative xenografts. F(ab')2fragments of NA1/34 displayed a faster clearance time of 19.6h compared with the intact antibody, 122.4 h, resulting in a more rapid maximum xenograft uptake time of 5h compared with 48 h postinjection for the intact antibody. Although the overall xenograft/tissue ratio for the F(ab')2 was at no time greater than that for the intact antibody, the F(ab')2 did display dramatically greater xenograft/blood ratios, reaching 19:1 at 120h postinjection Xenograft regression using single doses of 350μCi and 500μCi 131I-labeled NA1/34 significantly (p<0.001) delayed xenograft progression compared with control nonirradiated xenografts, with average delays of 3.2 and 5.7 times the control, respectively. This study suggests that the anti-CD1a monoclonal antibody, NA1/34, offers advantages in the prognosis and staging of Langerhans cell histiocytosis, in a human setting. We discuss the advantages of radioimmunoscintigraphy over conventional differential diagnostic techniques. The potential for the future radioimmunotherapy of Langerhans cell histiocytosis is also discussed.
Titel: |
Diagnostic and therapeutic evaluation of an anti-langerhans cell histiocytosis monoclonal antibody (NA1/34) in a new Xenograft model
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Autor/in / Beteiligte Person: | MURRAY, S ; ROWLINSON-BUSZA, G ; MORRIS, J. F ; CHU, A. C |
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Quelle: | International Workshop on Langerhans CellsJournal of investigative dermatology 114(1):127-134; Jg. 114 (2000) 1, S. 127-134 |
Veröffentlichung: | Danvers, MA: Nature Publishing, 2000 |
Medientyp: | Konferenz |
Umfang: | print, 42 ref |
ISSN: | 0022-202X (print) |
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