Product pipeline: P53

P53 is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor protein and is continuously produced and degraded in healthy cells. The p53 protein has been described as "the guardian of the genome", referring to its role in conserving genomic stability by preventing genome mutation.

P53 has many anti-cancer mechanisms:

• It can activate DNA repair proteins when DNA has sustained damage
• It can hold the cell cycle at the G1/S regulation point on DNA damage recognition allowing DNA repair proteins to fix the damage and the cell to continue the cell cycle
• It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable

P53 can induce growth arrest, apoptosis and cell senescence. In normal cells p53 is usually present at very low levels, bound to the protein MDM2 (HDM2 in humans), which prevents its action and promotes its degradation by acting as ubiquitin ligase. Over-expression of p53 is induced as an effect of various cancer-causing agents such as UV radiation, oncogenes and some DNA-damaging drugs. More than 50 percent of human tumors contain a mutation (see table) or deletion in the p53 gene, mostly leading to over-expression of the (mutated) p53 protein, offering the possibility to target p53 as a vaccine target.

ISA-P53-01 is a SLP vaccine consisting of 10 synthetic long peptides (25-30 amino acids) derived from the human P53 protein. Currently, the peptides are administered in a similar formulation as the HPV-SLP -vaccine, using Montanide-ISA-51 as adjuvant. The vaccine has been studied extensively in preclinical experiments and currently is in phase I/II studies in both colorectal and ovarian cancer.