Diagnostic and therapeutic evaluation of an anti-Langerhans cell histiocytosis monoclonal antibody (NA1/34) in a new xenograft model

Scintigraphy using monoclonal antibodies has been suggested as a possible a djunct to conventional staging techniques for the routine staging and diagn osis of Langerhans cell histiocytosis. In this study we have developed a mo del for Langerhans cell histiocytosis comprising a CD1a-positive subcutaneo us xenograft in the flanks of nude (nu/nu) mice. The anti-CD1a murine monoc lonal antibody NA1/34 was investigated for its potential both as an imaging and as a therapeutic targeting agent in this model. Biodistribution with N A1/34 compared with irrelevant isotype-matched monoclonal antibody demonstr ated specific accumulation within the xenografts of 10.0%id per g (percenta ge injected dose per gram) and 3.3%id per g at 48 h postinjection, respecti vely. NA1/34 displayed no specific accumulation to CD1a-negative xenografts . F(ab')(2) fragments of NA1/34 displayed a faster clearance time of 19.6 h compared with the intact antibody, 122.4 h, resulting in a more rapid maxi mum xenograft uptake time of 5 h compared with 48 h postinjection for the i ntact 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 1 20 h postinjection Xenograft regression using single doses of 350 mu Ci and 500 mu Ci I-131-labeled NA1/34 significantly (p < 0.001) delayed xenograft progression compared with control nonirradiated xenografts, with average d elays of 3.2 and 5.7 times the control, respectively. This study suggests t hat the anti-CD1a monoclonal antibody, NA1/34, offers advantages in the pro gnosis and staging of Langerhans cell histiocytosis, in a human setting. We discuss the advantages of radioimmunoscintigraphy over conventional differ ential diagnostic techniques. The potential for the future radioimmunothera py of Langerhans cell histiocytosis is also discussed.