Development of Genetic Vaccines for Treatment of Multiple Myeloma

The strategy is to develop DNA vaccines encoding tumour antigens expressed by neoplastic cells in multiple myeloma. The initial focus has been on the secreted idiotypic antigen. The VH and VL genes used to encode the idiotypic determinants have been assembled as a single chain Fv (scFv) in a pcDNA3 vector.

In a mouse model of myeloma, which closely resembles human myeloma in having osteolytic lesions and neoplastic plasma cells which are surface Ig-negative, scFv sequence alone is poorly immunogenic. However, fusion of a gene encoding a fragment of Tetanus toxin to the scFv sequence promotes the immune response against idiotypic determinants, and induces protective immunity. Protection appears to be mediated via CD4+ T-cells.

These results have set the scene for a small clinical trial. Currently we are engaged in a trial using a similar vaccine construct against lymphoma. If the results of this are promising, we shall move quickly to test the DNA vaccine in myeloma. The immune status of patients with myeloma is being investigated.

We are also analysing the use of other antigens expressed by myeloma cells, including the MUC-1 antigen. In collaboration with Professor Joyce Taylor (ICRF) we are developing a DNA vaccine to include MUC-1 sequence. We are examining expression of MUC-1 antigen by patients plasma cells.

Genetic VaccinesThe current status of this research program can be found on Prof. Freda Stephenson's Genetic Vaccines Against Cancer page at the University of Southampton School of Medicine.

Immunogenetics of Myeloma

We have an ongoing interest in the usage of VH and VL genes by neoplastic cells in myeloma. The pattern of somatic mutation is being used to follow the clonal history of the tumour cell clone. The are interesting differences between myeloma and MGUS which would be consistent with derivation of MGUS from a B cell at a less mature stage of differentiation.

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