Anti-tumor immunity induced by CDR3-based DNA vaccination in a murine B-cell lymphoma model.
The idiotypic structure present on B-cell neoplasms is a tumor-specific antigen and an attractive target for immunotherapy. Here, the tumor protective effects recruited by CDR3-based DNA vaccines in the poorly immunogenic, highly aggressive 38C13 murine B-cell lymphoma model were evaluated. The regions belonging to the idiotypic V(H) and V(L) CDR3 sequences were chosen for the design of two synthetic mini-genes and arranged in high-level expression plasmids. Syngeneic C3H/HeN mice were immunized by intramuscular electroporation with pV(H)CDR3-IL-2 and pV(L)CDR3-IL-2 naked DNAs. This approach provided protection in about 60% of animals challenged with a 2-fold lethal dose of tumor cells, as opposed to non-survivors in control groups. Furthermore, a long-term survival was induced in these mice since they were still alive and tumor-free 4 months following tumor challenge. Analysis of the humoral immunity revealed the presence of antibodies reactive with the peptides encompassing the CDR3 sequences in the sera of vaccinated mice. Moreover, immune sera specifically reacted with the parental 38C13 tumor cells in flow cytometry assays, indicating that such immunization elicited anti-idiotypic antibodies. These findings provide a basis for exploring the use of CDR3-based DNA vaccines against B-cell lymphoma.
Rinaldi
Monica
M
Institute of Neurobiology and Molecular Medicine, CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy. monica.rinaldi@artov.inmm.cnr.it
Fioretti
Daniela
D
Iurescia
Sandra
S
Signori
Emanuela
E
Pierimarchi
Pasquale
P
Seripa
Davide
D
Tonon
Giancarlo
G
Fazio
Vito Michele
VM
D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D019444:Vaccines, DNA