DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin
induce protective immunity against lymphoma and myeloma
Catherine A. King, Myfanwy B. Spellerberg, Delin Zhu, Jason Rice, Surinder S. Sahota, Andrew R. Thompsett, Terry J. Hamblin, Jiri Radl
& Freda K. Stevenson
Molecular Immunology Group, Tenovus Laboratory, Southampton
University Hospitals Trust, Southampton SO16 6YD,
England
Correspondence should be addressed to Freda K. Stevenson fs@soton.ac.uk
Vaccination with idiotypic protein protects against B-cell lymphoma,
mainly through anti-idiotypic antibody. For use in patients, DNA vaccines
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 design also induces protective immunity against
a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen
sequence allows a tumor antigen to engage diverse immune mechanisms that suppress
growth. This fusion design has the added advantage of overcoming potential
tolerance to tumor that may exist in patients.
