Researchers assessing AustCancer Phase II vaccine trial

Perth-based cancer therapeutics company Australian Cancer Technology (ASX: ACU) announced today that researchers at St Vincent's Hospital, Sydney have begun analysing results from the first group of patients in its Phase Ib/IIa clinical trial of its Pentrix vaccine for common cancers.

AustCancer has advised the ASX that interim results should be available by early next month. Up to 16 patients will be recruited by the end of the year.

The AustCancer announcement said it could take three months to determine whether a patient is a suitable candidate for its experimental antibody-based therapy.

Prof Robin Ward's research team at St Vincent's has been recruiting patients who have had surgery, or conventional radio- and chemotherapy, for various common cancers, including colorectal, prostate, renal, lung, head and neck and oesophageal cancers.

The patients have all been diagnosed with cancers that involve mutations that disrupt the function of a major tumour-suppressor gene called P53.

AustCancer MD Dr Alistair Cowden said the vaccine consisted of small peptide molecules whose shapes mimic those of mutant regions of the P53 molecules - the vaccine incorporates eight peptides that collectively span the most common mutations.

The immune system recognizes the Pentrix peptides as alien, and mounts an antibody response against the molecules. The same antibodies also recognize and bind to the mutant P53 proteins on cancerous cells, flagging them for destruction by hunter-killer T-cells.

Cowden said Nature Genetics reported proof-of-principle in a mouse model several years ago; if the St Vincent's trial results confirmed the presence of antibodies to the Pentrix vaccine, it would be the first demonstration of the feasibility of the approach as a broad-spectrum therapy for human cancers.

He said early indications were that the vaccine was well tolerated by patients, and should be harmless to normal cells - conventional radiation therapy and chemotherapy also kill rapidly dividing normal cells in bone marrow, and hair-root cells.

"If it works, it will be very significant," Cowden said. "P53 is a very famous molecule, and people have been trying for years to develop an antibody therapy against mutant P53, without success. We hope Pentrix will be the breakthrough."

P53 is mutated in at least 50 per cent of all cancers. It functions as a sentry, monitoring DNA damage; when a cell accumulates a potentially dangerous mutation load, P53 activates a genetic cascade that causes apoptosis - programmed cell death.

P53, in effect, instructs pre-cancerous cells to commit suicide before they can multiply out of control and form invasive tumours. But P53 is itself susceptible to mutation; the presence of P53 mutations in at least 50 per cent of common cancers suggests that loss-of-function mutations that disrupt the normal activity of so-called 'guardians of the genome' are often the final genetic insults that tip pre-cancerous cells over the edge, into cancerous growth.

The most common P53 mutations do not silence the gene; rather, they cause it to over-produce molecules of mutant P53 protein that cannot transmit the 'die now' signal to the pre-cancerous cell.

As an internal signalling molecule, P53 is normally invisible to the immune system, but cancerous cells tend to display mutant P53 molecules on their surface. AustCancer's Pentrix vaccine seeks to exploit this fact, by programming the immune system to recognize and destroy any cell displaying mutant P53 molecules.

The approach is potentially revolutionary because, if successful, it would provide a generic defence against at least 50 per cent of common cancers involving P53 mutations.