The L1 cell adhesion molecule as a target for radioimmunotherapy

Monoclonal antibodies directed against the L1 cell adhesion molecule were shown recently to inhibit growth of target tumor cells in vitro and the growth of tumor cells in vivo in nude mice. The biologic functions of L1 in tumor cells, which include growth-promoting activity linked to endocytosis and cellular processing of the L1 cell surface protein, make this protein an attractive target for antibodies. This update deals with recent results on L1 expression in normal tissues and in the tumors that were investigated until now. L1 expression outside of the nervous system is highly restricted to peripheral nerve bundles and kidney-collecting tubule cells. In tumors, L1 overexpression is not ubiquitous. It is prevalent in neuroblastomas and in malignant ovarian tumors, and is also found in certain subtypes of other nonneuroendocrine and nongynecologic tumors, such as renal-cell carcinomas. The structure of the L1 protein and what is known about its functional role in tumors will be described in this paper. L1 is not only a novel tumor marker, but it appears to have growth-promoting and antiapoptotic functions and may contribute to a more malignant phenotype. The preclinical studies and the clinical study to evaluate tumor-targeting properties and potential for therapy of radiolabeled anti-L1 antibodies will be described to date. Some of these studies underline the importance of L1 endocytosis for the targeting of radiolabeled antibodies.