Anti-idiotypic DNA vaccines for lymphoma immunotherapy require the presence of both variable region genes for tumor protection.
Vaccination with immunogenic formulations of lymphoma-derived immunoglobulin can elicit strong anti-idiotypic immune responses which have proved effective in murine B cell tumor challenge experiments and suggested possible benefits in recent human clinical trials. Naked plasmid DNA vaccines encoding the Id determinants as scFv fragments provide the most promising alternative to protein immunization. With this approach the addition of an immunogenic domain linked to the scFv has proved essential for the induction of a protective immune response. In this study we have produced a scFv gene construct linked to the CH3 exon of the human IgG1 constant region and tested its efficacy in inducing protective immunity against the mouse BCL1 lymphoma. We have also generated a second construct in which the BCL1 VL gene was deleted to investigate whether the VH region domain contains sufficient antigenic determinants for a protective immune response. Both constructs induced anti-idiotypic antibodies that specifically reacted with the BCL1 IgM protein in ELISA and with BCL1 tumor cells in flow cytometry assays. Protection against tumor challenge was fully achieved with the complete scFv construct whereas immunization with the construct lacking the VL gene resulted in only a slight prolongation of the survival. We therefore conclude that a plasmid DNA vaccine containing the VH and VL genes of the lymphoma Ig linked to the human IgG1 CH3 exon is highly effective in inducing a protective immune response in the BCL1 model. We also demonstrated that VH gene immunization can induce strong anti-idiotypic antibody responses.
Benvenuti
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F
International Centre for Genetic Engineering and Biotechnology, Area Science Park, Trieste, Italy.
Burrone
O R
OR
Efremov
D G
DG
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics*; D002460:Cell Line; D016172:DNA Fingerprinting / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005818:Genetic Engineering / Q000379:methods; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000888:Antibodies, Anti-Idiotypic; D007135:Immunoglobulin Variable Region; D019444:Vaccines, DNA