New strategies for vaccination and imunomodulation in NHL.

Knowledge of the genetic changes which occur in cancer cells is stimulating research aimed towards new therapies. Immunotherapeutic approaches, particularly antibody therapy, are already finding a place in treatment of hematological malignancies. Vaccination will build on experience in the field of infectious diseases, and it should be possible to design vehicles to deliver the expanding range of tumour antigens to the immune system. For DNA vaccines, fusion genes have the potential to activate and direct immune effector pathways. One candidate antigen for B-cell malignancies is the clonal idiotypic immunoglobulin and we have designed a fusion vaccine encoding idiotypic sequence fused to a sequence from a powerful antigen from tetanus toxin. This promotes protective immunity against lymphoma in models, and is now in clinical trial. One challenge is to bring patients into remission without significant damage to immune capacity. Another is to rethink the nature of clinical trials so that more pilot studies of efficacy can be carried out. There is no evidence so far of toxicity due to injection of DNA, but for antigens which are expressed by normal cells, the line between attack on tumour and autoimmunity will have to be carefully drawn.