RADIOIMMUNOTHERAPY OF SMALL-CELL LUNG-CANCER XENOGRAFTS USING I-131-LABELED ANTI-NCAM MONOCLONAL-ANTIBODY 123C3

We have studied the therapeutic efficacy of I-131- labelled monoclonal antibody 123C3 in human small-cell lung carcinoma xenografts establis hed from the NCT-H69 cell Line in nude mice. Several radiation doses w ere administered intraperitoneally and different treatment schedules w ere tested. The maximal tolerated dose, 2 x 500 mu Ci, resulted in com plete remission of tumours smaller than 200 mm(3) and long-lasting rem ission (more than 135 days) of the larger tumours. In control experime nts, treatment with unlabelled monoclonal antibody 123C3 did not affec t the tumour growth rate, while the effect of radiolabelled non-releva nt, isotype-matched, monoclonal antibody M6/1 was minor and transient. Regrowth of the tumours occurred in all cases and could not be attrib uted to loss of neural cell adhesion molecule (NCAM) expression. Tumou r recurrence is probably caused by insufficient radiation dosage. Radi ation-induced toxicity was monitored by assessment of weight and bone marrow examination. Weight loss was observed in all treatment groups, but the mice regained their initial weight within 14 days, except for the group receiving the highest radiation dose (3 x 600 mu Ci). In thi s group all mice died as a result of radiotoxicity. Of the mice inject ed with 600 mu Ci radiolabelled control antibody, 50% died within 2 we eks after administration. Apparently the higher uptake of the radiolab elled monoclonal antibody in the tumour reduced systemic radiation tox icity.