The long range goal of these studies is to develop criteria for predicting which B cell-reactive monoclonal antibodies will have anti-tumor effects 1) by themselves, 2) in combination with each other and 3) in combination with B cell-reactive immunotoxins and/or chemotherapy. There is accumulating evidence that potent antibody-mediated anti-tumor effects can be achieved by either apoptosis and/or cell cycle arrest. In a human Burkitt's lymphoma line, anti-CD19 induces lyn-dependent cell cycle arrest. In contrast, the crosslinking of IgM induces apoptosis. We will use these two different effects to screen monoclonal antibodies against epitopes on four candidate antigens that appear to transmit negative signals to tumor cells, i.e., CD20, 21, 23 and 24. Our major objective is to identify an antibody that causes apoptosis (since anti-mu cannot be used clinically) and to determine whether there are additive effects among these signalling antibodies based on their categorization in vitro. The objective is to develop an in vitro paradigm for predicting the efficacy of combinations of antibodies by themselves or with chemotherapy and/or immunotoxins so that clinical trials can be designed rationally rather than on a hit-or-miss basis.
