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Studies on tumour antigens associated with human bronchogenic carcinomata Watson, Robert Dale

Abstract

Bronchogenic carcinomata of various pathologies were obtained either at post-mortem or post surgically for the purpose of this study. Normal lung tissue as control material was obtained from individuals who died-from non-malignant causes. Antigenic materials were extracted from both normal and tumour tissue with 3.0 M KCl in order to determine whether bronchogenic tumours contained either tumour specific transplantation antigens (TSTA -cell surface antigens recognized as non-self by the host immune system) or tumour associated antigens (TAA - components not found in normal tissue which may or may not be antigenic in the host but which are antigenic in a heterologous species). Attempts to identify tumour associated antigens by direct chemical comparisons between normal and tumour extracts were made using disc gel electrophoresis in conjunction with ion exchange and gel filtration chromatography of the extracts. A tumour associated antigen was detected in this way but it was not found in other tumour extracts and therefore its significance was limited. Autoradiographic studies using sections of tumour or normal lung, patients' or normal sera, and ¹²⁵I-labelled anti-human Ig indicated that patients with bronchogenic carcinoma may produce antibodies reactive with their own and other tumours. Skin test reactions to fractions of homologous tumour extract also suggested that patients may react to tumour antigens, but neither of these methods were found to be suitable as an assay for tumour antigens. Efforts to raise antisera against tumour antigens by rendering rabbits neonatally tolerant to normal lung antigens followed by immunization with tumour extract proved unsuccessful. Greater success was obtained by hyperimmunizing rabbits to tumour extracts and passing resultant antisera through solid immunoadsorbents of normal lung extracts. The absorbed antisera, in many instances, reacted specifically with antigens in tumour extracts. Broad studies using immunodiffusion with absorbed antisera and a panel of tumour extracts indicated that bronchogenic carcinomata may contain at least two tumour associated antigens which cross-react widely. One of these antigens appeared to share properties with an antigen in foetal lung extracts, but was neither carcinoembryonic antigen nor α₁-foetoprotein. When summarized, the results suggested that some TAA were associated with tumour pathology and possibly aetiology; squamous cell, oat cell and anaplastic carcinomas (carcinogen induced) appeared to contain related TAA which were distinguished from TAA in adenocarcinomas and alveolar cell carcinomas (not known to be associated with carcinogens).

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