Vaccine therapy in NHL: future promises and current limitations.

Recent advances in genomics are revealing new molecular targets for vaccination strategies in cancer, and unraveling the immune pathways that must be activated. Initially, work focused on idiotypic antigen expressed by the clonal immunoglobulin (Ig) of B-cell tumors. This involved assembling the encoding V(H) and V(L) genes as single-chain Fv (scFv), which has been fused to Fragment C (FrC) of tetanus toxin to enhance recognition and response. The fusion gene induces strong anti-idiotypic protection against lymphoma in experimental models, and is now in clinical trials with encouraging results emerging. This principle of fusing a pathogen-derived sequence is widely applicable. A coat protein from a potato virus substituted for the FrC sequence has also been found to be capable of promoting anti-tumor immunity. The current design is effective in inducing anti-idiotypic (Id) antibody and CD4+ T-cell attack. For intracellular tumor antigens expressed as MHC Class I-associated peptides, a design consisting of a gene encoding a single domain of FrC linked to a candidate peptide sequence has been developed. This induces fast cytotoxic T-cell attack on peptide-expressing tumor cells. Injection of DNA appears safe and clinical trials will test the efficacy of this approach, and probably lead to improvements in these flexible vaccines.