Idiotype-encoding recombinant adenoviruses provide protective immunity against murine B-cell lymphomas.
Vaccination with tumor-specific immunoglobulin or idiotype (Id) is a promising new form of immunotherapy for B-cell malignancies. Id protein vaccination has demonstrated clinical activity in B-cell lymphomas, yet it requires the laborious and time-consuming procedures of tumor-myeloma cell hybridization, large-scale in vitro culture, and protein purification. Recombinant adenoviruses are highly efficient and immunogenic gene transfer vehicles from which individualized vaccines can be rapidly assembled using polymerase chain reaction-amplified tumor Id genes. Id-encoding adenoviruses were evaluated as vaccines in 2 murine B-cell lymphoma models. A single injection of recombinant Id adenovirus provided protection from subsequent tumor challenge that was equivalent or superior to that afforded by Id protein vaccination. Protected mice had substantial serum titers of Id-specific antibodies. When used in conjunction with chemotherapy, vaccination also prolonged the survival of mice bearing pre-existing tumor. Mechanistic studies demonstrated that tumor protection was not dependent upon T cells. Importantly, in mice prevaccinated with an irrelevant adenovirus, tumor protection following vaccination with Id adenovirus was not significantly impaired. These findings have implications for the design of future lymphoma immunotherapy trials.
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
J M
JM
Timmerman
C B
CB
Caspar
S L
SL
Lambert
A D
AD
Syrengelas
R
R
Levy
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D016393:Lymphoma, B-Cell / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage*; D001613:beta 2-Microglobulin / Q000235:genetics
D007130:Immunoglobulin Idiotypes; D019444:Vaccines, DNA; D001613:beta 2-Microglobulin