DNA VACCINES WITH SINGLE-CHAIN FV FUSED TO FRAGMENT-C OF TETANUS TOXIN INDUCE PROTECTIVE IMMUNITY AGAINST LYMPHOMA AND MYELOMA

Vaccination with idiotypic protein protects against B-cell lymphoma, m ainly through anti-idiotypic antibody. For use in patients, DNA vaccin es containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion de sign also induces protective immunity against a surface Ig-negative my eloma. These findings indicate that fusion to a pathogen sequence allo ws a tumor antigen to engage diverse immune mechanisms that suppress g rowth. This fusion design has the added advantage of overcoming potent ial tolerance to tumor that may exist in patients.