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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1370-1377
NEOPLASIA
Idiotype-encoding recombinant adenoviruses provide protective
immunity against murine B-cell lymphomas
John M. Timmerman,
Clemens
B. Caspar,
Stacie L. Lambert,
Athanasia D. Syrengelas, and
Ronald Levy
From the Division of Oncology, Department of Medicine,
Stanford University School of Medicine, Stanford, CA.
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.
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