In this project we will continue clinical trials of monoclonal antibodies in human lymphoma. We will focus on B cell lymphoma using custom-made anti-idiotype antibodies since this is the area in which the best results have so far been obtained. Refinements will be made in patient selection, antibody development and production and mode of antibody administration in order to take advantage of the information generated in our earlier trials and to improve the clinical results. The clinical and biological correlates of tumor response will be defined by studies on the antibodies, the tumor and the host. Each patient's tumor will be studied for genetic heterogeneity by immunoglobulin gene rearrangements and by multiple different anti-idiotype antibodies. In this way, we hope to continue to gain insights into the biology of human lymphoid malignancy.