Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analyses with monoclonal antibodies.

Cloned cell lines and a number of subclones from these lines were established in vitro from biopsies of small cell lung carcinomas and squamous cell lung carcinomas. The cloned cultures, including the cloned subclones, were analyzed in respect to morphology, karyotype, growth rates, clonogenicity in semisolid agar medium, and tumorigenicity in nude mice. A remarkable biologic diversity was found in respect to most of these biologic features. In addition, four murine monoclonal antibodies with high specificity for lung tumor cells were generated. Their reactivity pattern to clonogenic cells was for some clones different as compared to the nonclonogenic cells. Subclones of tumor cells not binding the antibody were identified for each monoclonal antibody. It is concluded that intratumoral phenotypic diversity may have a severe negative impact on the use of monoclonal antibodies in cancer diagnosis/therapy. The work also indicates that a mixture of antibodies may be more useful in tumor diagnosis than individual antibodies and perhaps even therapy, particularly if they bind to the clonogenic part of a cell population.