AustCancer claims good results in prostate trial

Cancer therapeutics company Australian Cancer Technology (ASX:ACU) announced today its GPI-0100 vaccine adjuvant has produced an enhanced immune response in its Phase I clinical trial in men with relapsed prostate cancer.

The trial, the first to test AustCancer's immunostimulatory molecule in human cancer patients, involves patients with progressive prostate disease after primary surgery or radiotherapy.

Although they have no evidence of cancer, the patients have rising serum levels of PSA (prostate-specific antigen), a key diagnostic marker for prostate cancer.

The trial, led by Dr Susan Slovin, assistant professor of medicine at the Memorial Sloan Kettering Cancer Centre in New York, involves a dose-escalation study to determine the optimal and safe range of the GPI-0100 adjuvant when used in combination with a two-component vaccine.

The vaccine contains two antigens over-expressed by prostate tumours -- MUC-2 and Globo. Both antigens are coupled to a molecule called KLH to enhance their immunogenicity.

Cohorts of five patients were vaccinated with the same amount of the two antigens, but with escalating doses (100, 300, 1000 and 3000 micrograms) of the GPI-0100 adjuvant to assess its safety. Subsequently, another 14 patients were treated with the same vaccine, but with a more purified form of the adjuvant, at doses of 1000, 3000 and 5000 micrograms.

For comparative purposes, another 9 patients were enrolled in a second trial using the same vaccine, but mixed with 100 micrograms of a saponin adjuvant, QS-21, extracted the bark of the South American soap bark tree Quillaja saponaria. GTPI-0100 is a semi-synthetic form of the saponin adjuvant.

AustCancer's CEO, Dr Paul Hopper, now based in San Francisco, said there was currently no standard of care for men with rising PSA levels after the failure of primary therapy.

Hopper said all the vaccines containing GPI-0100 were found to be safe. Overall, the adjuvant had produced significant less pain and inflammation at the injection sites, and fewer systemic symptoms, compared to those who had received QS-21, who had similar antibody titres.

The trial indicated that GPI-0100 is safe, and stimulates a strong immune response, warranting its further use in vaccine studies, according to the company.

AustCancer said GPI-0100's superior stability and safety profile made it an ideal candidate for developing novel therapeutic or preventative vaccines.

Sloan-Kettering researchers are planning to trial GPI-0100 as adjuvant for therapeutic vaccines for melanoma, neuroblastoma, breast cancer, ovarian cancer and chronic myeloid leukaemia.

Another Phase I trial at the University of Alabama Comprehensive Cancer Centre in Birmingham is currently evaluating GPI-0100 in combination with the HER-2 vaccine for breast cancer.

Last week AustCancer announced it had almost completed recruiting patients for its Australian-based Phase IIb study of its Pentrys anti-cancer vaccine in prostate-cancer patients. To date, it has enrolled and treated 36 of a planned 40 patients. Only 22 patients have currently reached the 17-week mark, and the company says the data are "too immature" to derive any meaningful results.

The Pentrys vaccine contains synthetic antigen 'mimics' of a mutant protein, P53, expressed on the surface of more than 50 per cent of all solid tumours. The P53 gene, dubbed 'guardian of the genome', is one of the master genes in apoptosis -- it monitors dividing cells for mutations, and initiates their self-destruction before they turn cancerous. Mutations in P53 itself are often one of the final events in the development of cancer.

When P53 mutates, the mutant protein fragments are translocated from the interior of the cell and displayed on its surface, identifying the cell as cancerous. The Pentrys vaccine is designed to elicit antibodies to the mutant proteins, that will mark the cancerous cells for destruction.

Hopper said enrolments should be completed by the end of March, and results are expected before the end of the year.

The multi-centre trial is being conducted at Melbourne's Austin Hospital, the Royal Melbourne Hospital, and the Peter MacCallum Cancer Centre.