Immunotargeting of human small cell lung cancer xenografts in athymic mice using a monoclonal antibody (RNL-1) against a neuroendocrine-related antigen

Abstract

A mouse monoclonal antibody (RNL-1) was raised against the variant small cell lung cancer (SCLC) cell line NCI-H82. Immunohistochemical studies on frozen sections showed that the antibody was reactive with most SCLC (15 out of 16) and lung carcinoids (six out of seven), while in general adenocarcinomas and squamous cell carcinomas of the lung were negative. Immunocytochemical studies on 29 different cell lines derived from human lung tumours confirmed the neuroendocrine-related expression of the RNL-1 defined antigenic determinant. Immunoelectron microscopy showed that RNL-1 recognises an extracellular membrane domain, concentrated at adhesion sites between adjacent cells. The tissue distribution of the RNL-1 defined antigen was mainly restricted to neural and neuroendocrine tissues. These immunohistochemical data suggest that RNL-1 is directed against a neuroendocrine-related cell adhesion molecule. Being reactive with an epitope expressed on the surface of most neuroendocrine malignant cells, RNL-1 (IgG1 isotype) is a potential vehicle for targeting SCLC in vivo. We evaluated the ability of radiolabelled RNL-1 to localise human SCLC xenografts in nude mice as a first step in determining the in vivo value for radioimmunodetection. RNL-1 was radioiodinated using the Bolton-Hunter labelling technique. Nude mice bearing NCI-H82 xenografts were injected intravenously with the radiolabelled RNL-1 preparations, and animals were dissected 4, 24, 48, 72 and 120 h post injection (p.i.) to determine the biodistribution of the radiolabel. The iodine-125 label accumulated in the tumour up to 48 h p.i. (6.5% injected dose per gram of tissue [ID g-1]), while the label content of the normal tissues decreased with time.(ABSTRACT TRUNCATED AT 250 WORDS)