Product pipeline: Colorectal Cancer

Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. Surgery is the primary form of treatment and results in cure in approximately 50% of the patients. However, recurrence following surgery is a major problem and is often the ultimate cause of death. Within 5 years some 45% of all colorectal cancer patients die despite treatment. This makes colorectal cancer the third most common cancer and the second most frequent cause of death due to cancer.

As in many other types of cancer, the tumor-associated self-antigen p53 is over-expressed in colorectal cancer. In cancer cells loss of wild-type p53 function e.g. by p53 mutations may lead to more aggressive tumor growth, failure to respond to standard therapy and poor prognosis. Different expression levels of p53 in tumor cells compared to normal cells provide an immunological window for p53 wild-type (wt) specific immune effector cells. In other words, different expression levels of p53 in tumor cells results in different numbers of wt-p53 derived T cell epitopes in MHC molecules and possibly also in other epitopes compared to normal cells, providing T cells the immunological window to discriminate between tumor cells and normal cells. Mutant and wild-type p53 specific CTL have been described in mice.

Through ISA's approach, using synthetic long peptides encoding the p53 protein itself instead of short MHC binding peptides, p53-specific CTL and Th responses against dominant and cryptic MHC class I and II peptides will be induced that are not limited by the HLA type of the patient.