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, 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.
King
C A
CA
Tenovus Laboratory, Southampton University Hospitals Trust, England.
Spellerberg
M B
MB
Zhu
D
D
Rice
J
J
Sahota
S S
SS
Thompsett
A R
AR
Hamblin
T J
TJ
Radl
J
J
Stevenson
F K
FK
D000818:Animals; D019496:Cancer Vaccines; D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013160:Splenic Neoplasms / Q000628:therapy*; D013744:Tetanus Toxin / Q000276:immunology*; D019444:Vaccines, DNA
D019496:Cancer Vaccines; D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D019444:Vaccines, DNA; C040635:tetanus toxin fragment C