Monoclonal antitumor antibodies in the lymphatics.

Monoclonal antitumor antibodies are being administered iv in a number of medical centers for diagnosis or therapy of human cancers. However, when the objective is to detect or to treat tumor in regional lymph nodes, sc injection may prove more effective. After sc injection, monoclonal antibodies enter local lymphatic capillaries, pass to the draining lymph nodes, and bind to target cells there. Antibody not bound in the first node group encountered passes to more distant nodes. If still not removed from the lymph flow, antibody passes into the bloodstream, principally through the thoracic duct. Initial studies of the lymphatic approach were done with antibodies directed against antigens on normal cell types in the mouse lymph node. The use of antibodies to normal cells made it possible to study the pharmacokinetics of delivery in a reproducible, quantitatively interpretable system. The pharmacologic models developed were then applied to the design of experiments on line 10 hepatocarcinoma of guinea pigs. As little as 2 mg of line 10 tumor could be identified by gamma camera imaging in regional nodes after injection of 125I-labeled antibody. The uptake was immunologically specific, and autoradiography showed localization exclusively within the metastatic tumor. When the aim is to diagnose or treat early tumor metastases in the nodes, the lymphatic route can be expected to provide higher sensitivity, lower background, lower systemic toxicity, and faster localization than the iv route. Perhaps most interesting, the lymphatic route minimizes exposure of antibody to cross-reactive antigen present on normal tissues elsewhere in the body. Antitumor antibodies rejected for iv use because they also bind to normal tissues may, therefore, be useful in the diagnosis and treatment of lymph node metastases.