Radioimmunotherapy of small-cell lung cancer xenografts using 131I-labelled anti-NCAM monoclonal antibody 123C3.
We have studied the therapeutic efficacy of 131I-labelled monoclonal antibody 123C3 in human small-cell lung carcinoma xenografts established from the NCI-H69 cell line in nude mice. Several radiation doses were administered intraperitoneally and different treatment schedules were tested. The maximal tolerated dose, 2 x 500 microCi, resulted in complete remission of tumours smaller than 200 mm3 and long-lasting remission (more than 135 days) of the larger tumours. In control experiments, treatment with unlabelled monoclonal antibody 123C3 did not affect the tumour growth rate, while the effect of radiolabelled non-relevant, isotype-matched, monoclonal antibody M6/1 was minor and transient. Regrowth of the tumours occurred in all cases and could not be attributed to loss of neural cell adhesion molecule (NCAM) expression. Tumour recurrence is probably caused by insufficient radiation dosage. Radiation-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 microCi). In this group all mice died as a result of radiotoxicity. Of the mice injected with 600 microCi radiolabelled control antibody, 50% died within 2 weeks after administration. Apparently the higher uptake of the radiolabelled monoclonal antibody in the tumour reduced systemic radiation toxicity.
Kwa
H B
HB
Department of Medical Oncology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Verhoeven
A H
AH
Storm
J
J
van Zandwijk
N
N
Mooi
W J
WJ
Hilkens
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019006:Neural Cell Adhesion Molecules / Q000276:immunology*; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019006:Neural Cell Adhesion Molecules