Cancer vaccines - Different approaches

It has been asked what the risk of creating autoimmune disorders would be from a cancer vaccine. Good question and its certainly a theoretical concern if you are training the immune system to target antigens that are also expressed on normal cells. It's unlikely to be a concern with Provenge, because prostate cells are the only ones expressing PAP, and the patient would have had the prostate already removed. It's more a concern with approaches such as Cell Genesys' GVAX or Antigenics' Oncophage which use cell lysates, i.e. mixtures of all antigens in the cell, most of which will be universal, rather than just one.

That said, it may be possible to create an immune response against a widely expressed antigen and still have it result in a therapeutic index > 1 if the antigen is more highly expressed in cancerous tissue and if the immune response is not too strong. This is what already seems to be occuring in passive immunotherapy, e.g. administration of anti-HER2 antibodies for breast cancer aka Herceptin aka Genentech's hot-selling drug. HER2 is by no means confined to breast cancer cells; its just more highly expressed in them. Given these complexities, I think it's safer to use the single antigen approach like Dendreon is doing because it allows testing of the therapeutic ratio of immune responses to a single trigger, rather than the throw everything at the wall and see what sticks approach of Cell Genesys or Antigenics. The latter could still work, but it is less predictable, I think.

Where else could a single-antigen approach work? Spontaneous immune-mediated remissions has often been seen with melanomas, which seem to be naturally antigenic, likely because melanocytes express several antigens that are not found in any other tissue and because the skin is full of dendritic cells that are ready to sound the alarm to the immune system if they smell something fishy. Anybody who has undergone allergy testing or has allergic dermatitis or eczema can attest to this. The fact that one can live without melanocytes makes melanoma like prostate cancer a good target for immunotherapy, and in fact there are many cancer vaccines under development for melanoma.