Abstract
Abnormally elevated expression of certain plasma proteins, cytokines, and cell surface molecules is found related to the development of certain diseases. Controlling the expression of these autologous molecules may be exploited as a means to control the progression of such diseases. The approach of using monoclonal antibodies specific for those autologous molecules as a new class of biopharmaceuticals for treating the affected diseases has been actively pursued and numerous successes have been achieved. However, the potential immunogenicity of the therapeutic antibodies may elicit antibody responses in the recipients and hence compromise the efficacy of such therapies. As an alternative, inducing active autoimmunity with specificity against disease-related autologous antigens in immunogenic forms has been evaluated as a feasible approach. Such therapeutic vaccines may be administrated in combination with antibodies or conventional chemotherapeutic agents. The induced autoantibodies may potentially improve therapeutic efficacy and prevent from elapses of these diseases.In this thesis, two different approaches have been demonstrated to induce auto-reactive/cross-reactive immunity with designed specificity: one, fusing peptides of autologous antigens with T cell epitopes based on foreign Fc, and two, homologous protein mimicry. Several B cell specific antigens, such as Ig□ (CD79a), Ig□ (CD79b) and CD20, have been explored to trigger T cell-dependent antibody responses in BALB/c mice. The induced auto-reactive/cross-reactive antibodies can recognize the targeted self antigens both in vitro and in vivo, and bind to cells of a mouse B cell line. The proportions of B cells in the peripheral blood of treated mice decreased, as compared to those of control mice immunized with irrelevant antigens. Furthermore, the treated mice also made reduced antibody response against a 2nd antigen, indicating the reduction of B cell biofunctions. The implications of employing the present concepts to develop a therapeutic approach for treating patients with B cell neoplastic diseases or with certain antibody-mediated autoimmune diseases are discussed.