The efforts of this Branch has been central to the recognition of gastrin releasing peptide as an autocrine growth factor for small cell lung cancer. Dr. Cuttitta developed a monoclonal antibody (2A11) to the active portion of that peptide and demonstrated that the immunoglobin could block the mitogenic effect of GRP in vitro and in vivo. We have recently, in collaboration with Hybritech, Inc. (San Diego, CA), initiated a clinical trial to test whether one can control autocrine mediated malignant proliferation of small cell lung cancer using a monoclonal antibody. Our Branch has a long standing interest in the role of growth factors in cancer, so that information from 2A11 antibody clinical trial could be a foundation from subsequent anti-growth factor trials. The phase I portion of the 2A11 antibody trial identified 250mg/m2 on the monoclonal as the optimal dose. The Phase II portion of the 2A11 evaluation has recently started. We have previously reported the diagnostic application of lung associated monoclonal antibodies derived at this Branch for use in the early detection of lung cancer. We have patented the method for this approach with collaboration from John Hopkins and in conjunction with the Lung Cancer Study group will proceed to rapidly follow up on this critical area. We have followed up on this work with several publications including a report characterizing the fine binding affinity of one of the antibodies used for early lung cancer detection. The proposed follow up trial should start this year.
