Indolent B-cell malignancies: immune recognition and antiself

B-cell malignancies appear to be ideal candidates for treatment with immunotherapeutic approaches. Monoclonal antibodies that target cell-surface determinants have been used as single agents in B-cell malignancies, in combination with chemotherapy, and coupled to other agents to create radioimmunoconjugates and immunotoxins. Another approach is to take advantage of the graft-vs.-lymphoma effect seen following allogeneic bone marrow transplantation. To exploit this effect without inducing the complication of graft-vs.-host disease, it is necessary to understand the mechanisms whereby lymphoma cells escape T-cell-mediated responses. CD40 activation may offer a means of increasing the immunogenicity of lymphoma cells and of stimulating allogeneic T-cell proliferation and cytokine production. Vaccination using tumor-specific antigens shows promise as a therapeutic strategy. Pre-clinical studies with immunoglobulin idiotype peptides have shown that humoral and cellular immune responses can be stimulated by antibodies to these peptides, but better tumor antigens need to be identified that can reliably generate cytotoxic T-cell responses. Candidate antigens include heteroclitic peptides from the immunoglobulin V region and newly identified antigens including the cytochrome P450 1B1. Clinical trials are ongoing in all these fields.