PROSPECTS FOR PREVENTING ALL CANCER

Abstract

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Cancer is a leading cause of death worldwide, killing ~8M people per year. Most of these deaths occur in the developing countries. In the US it is the leading cause of healthcare economic expense — ~$250B/year. It is estimated that the total cost worldwide is ~$1T/year and WHO predicts cancer will be of epidemic proportions in the developing world, largely due to increasing life expectancy and overwhelmed healthcare systems. Clearly, humans must deal with this problem. The prospects offered by the cancer research community are not encouraging in this regard. New forms of treatment (eg positron emission therapy) are marginally effective and increasingly expensive. They are a disappointment to those in the developed world and largely unavailable to those in the developing world. A new perspective and approach is required. In response to this dilemma we proposed developing a universal, prophylactic cancer vaccine. That is a vaccine that is given to everyone to prevent them from developing 31 РОССИЙСКИЙ ОНКОЛОГИЧЕСКИЙ ЖУРНАЛ, № 4, 2013 cancer. Most in the community have felt that this would not be possible because tumors are so variant a single vaccine could not be produced. Cancer is too personal. At the genomic level this is true, but we have found that at the RNA processing level this is not the case. Tumors recurrently make the same splicing errors and these errors result in frameshift variants. These frameshift (FS) variants mark the tumor as 'foreign' and open to immunological attack. However, to be effective as a vaccine these antigens must be presented to the immune system (the vaccine) before the tumor starts to develop. We put in place a process involving 1)bioinformatics screens of tumor cDNA libraries to find FS, 2) screening for the presence of the FS in the RNA of a tumor panel, 3) testing the FS as vaccines in mouse tumor models, and 4) screening human sera from cancer patients for reactivity to the FS. Based on this process we have gathered a collection of FS candidates for a human vaccine. We currently estimate that less than 20 elements will be needed to provide coverage for most cancers. When we initiated this project ~9 years ago, most in the field doubted such a vaccine could be made. More recently the opinion has shifted to that it may be possible to create such a vaccine but how would it ever be tested for efficacy. Many think the time and cost involved in Phase II/III trials would be insurmountable. However, we have developed a plan based on another invention, immunosignature diagnostics, which may overcome this problem. This technology is based on profiling the antibodies in an individual. It can detect disease, including cancer, early. Our proposal for a Phase II efficacy trial is that potential participants be prescreened for latent cancers. 1000 cancer free people would be entered into the control and vaccine arms of the trial. Individuals would be frequently monitored by immunosignatures for early signs of cancer. The endpoint would be fewer early events in the vaccine versus control arm after 2 years. Though a clear challenge, it seems feasible that such a vaccine could be developed. Because it could be inexpensive, all the world would benefit from such a vaccine.