Abstract

To characterize a single domain antibody (sdAb), AFAI, obtained by panning a naive phage display library of single domain antibodies against the non-small cell lung carcinoma cell line A549. AFAI recognizes a variant form of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 or CEA6). Various normal tissues and 139 neoplastic lesions from lung and other organs were immunostained with ES1 antibody, a pentameric and highly avid form of AFAI. ES1 was immunoreactive with 34 of 35 non-squamous large cell lung carcinomas with staining intensities ranging from focal to extensive and from moderate to strong. Importantly, ES1 stained poorly differentiated lung adenocarcinomas and many undifferentiated large cell lung carcinomas that typically show negative immunoreactivity with an antibody specific for thyroid transcription factor-1. Non-lung adenocarcinomas showed more focal and weaker immunoreactivity than for lung adenocarcinoma. Other carcinomas showed negative or weak immunoreactivity and normal tissues showed no immunoreactivity. Compared with other antibodies used in the clinical evaluation of lung adenocarcinomas, ES1 is more lung carcinoma sensitive, more sensitive in immunostaining of poorly differentiated adenocarcinomas that are usually associated with distant metastasis and less immunoreactive with normal tissues.

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