Cancer cells differ from normal cells and those differences are coded in the DNA. When the code is read it can lead to synthesis of tumour-associated proteins. Potentially, these can be perceived as foreign by the immune system of the host. However, once a patient has cancer, the immune system has failed. Our strategy is to repackage the tumour antigens in a vaccine format which can alert immune recognition and induce an effective anti-tumour immunity.

The first tumour we are investigating is B-cell lymphoma where there are many potential tumour antigens. Among the specialised proteins, the idiotypic determinants carried by the immunoglobulin provide a well-defined target for induction of immunity. However, new information from genome analysis is defining a myriad of additional target gene sequences. The same technology is applicable to prostate cancer where several target antigens have already been defined.

Our tumour vaccines are based on new technology developed for vaccines against infectious diseases. Instead of using killed or attenuated organisms, naked DNA which encodes particular antigenic proteins is being used. On injection into muscle or skin, the code is transcribed into RNA, which is translated into protein. The foreign protein then induces antibody and T-cell responses which attack the organism.

Our strategy for DNA vaccine construction relies on obtaining the sequence from the tumour cell which encodes a candidate antigen. Using polymerase chain reaction (PCR), we amplify the chosen gene and place it into a bacterial plasmid vector which consists of a circle of carrier DNA. Interestingly, the carrier DNA itself is immunostimulatory and sets the scene for the immune response.

Induction of immunity against cancer is more difficult than inducing protection against infectious organisms. Patients already have cancer, and may be tolerant to the antigens; they may have a damaged immune system due to the disease, or due to chemotherapy; and the tumour antigens may be weak. To promote recognition and activation of immunity we have fused a gene encoding a pathogen-derived protein to our tumour antigen sequence. The promotional sequence is derived from Tetanus Toxin, and is itself highly immunogenic. When fused to idiotypic antigens, it dramatically increases the anti-tumour response. We are currently conducting a PhaseI/II clinical trial of our idiotypic DNA fusion vaccines involving a small number of patients with follicular lymphomas, and clinical trials for patients suffering from multiple myeloma and chronic lymphocytic leukemia have been planned.

Prostate cancer expresses a number of tumour-associated antigens, such as prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP) and prostein, and we are exploring the same gene-based fusion vaccine strategy as a potential treatment for prostate cancer in our laboratory.