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Published on: October 18, 2012
A genetic approach to idiotypic vaccination
R E Hawkins1, G Winter, T J Hamblin
1MRC Laboratory of Molecular Biology and Centre for Protein Engineering, Cambridge, United Kingdom.
Treatment of cancer with vaccines is an attractive prospect, but few tumours express suitable target antigens. With B-cell lymphomas, the idiotypic immunoglobulin (Ig) of the malignant B-cell should provide a suitable target but this requires a vaccine to be created for each patient. We propose a strategy for making such vaccines: first to clone the V genes of the idiotypic Ig, and second to inject the patient with the cloned DNA (genetic immunisation) in order to elicit an immune response against the encoded Ig. We have previously shown that the V genes of the idiotypic Ig can be identified from human lymph node biopsies by polymerase chain reaction amplification, cloning, and sequencing. In this report, we show that anti-idiotypic antibodies can be elicited by direct injection of an expression vector that encodes the V genes of murine antibodies (the V genes of B1.8, a murine hybridoma or of BCL1, a murine lymphoma line). This finding suggests a simple approach to the preparation of idiotypic vaccines for patients with B-cell lymphoma, which also circumvents the need for adjuvants.
Treatment of cancer with vaccines is an attractive prospect, but few tumours express suitable target antigens. With B-cell lymphomas, the idiotypic immunoglobulin (Ig) of the malignant B-cell should provide a suitable target but this requires a vaccine to be created for each patient. We propose a strategy for making such vaccines: first to clone the V genes of the idiotypic Ig, and second to inject the patient with the cloned DNA (genetic immunisation) in order to elicit an immune response against the encoded Ig. We have previously shown that the V genes of the idiotypic Ig can be identified from human lymph node biopsies by polymerase chain reaction amplification, cloning, and sequencing. In this report, we show that anti-idiotypic antibodies can be elicited by direct injection of an expression vector that encodes the V genes of murine antibodies (the V genes of B1.8, a murine hybridoma or of BCL1, a murine lymphoma line). This finding suggests a simple approach to the preparation of idiotypic vaccines for patients with B-cell lymphoma, which also circumvents the need for adjuvants.
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