Anti-tumour effects demonstrated by CancerVax technology

CancerVax, from Carlsbad, CA, has produced data to demonstrate that treatment of mice with an 11-nucleotide T-oligo (telomere homologue oligonucleotide) inhibited melanoma tumour growth and reduced the size and number of metastases in preclinical studies.

Results also showed that in vitro treatment with this T-oligo selectively induced apoptosis of melanoma cells but not of normal human melanocytes (melanin-containing skin cells). The data support previously published data indicating that T-oligos may activate natural defence mechanisms to induce cell cycle arrest, differentiation or apoptosis in cancerous cells.

'The preclinical results obtained with T-oligos suggest that this technology may be used to develop therapies that use inherent biological processes to effectively target cancer cells without causing significant toxic effects in normal cells,' said David Hale, president and ceo of CancerVax. 'The T-oligo technology is an important component of our pipeline of biological treatments for cancer, which includes specific active immunotherapies, such as Canvaxin, which is in Phase III clinical trials in advanced-stage melanoma, and SAI-EGF, which targets epidermal growth factor and has been studied in Phase II clinical trials in non-small-cell lung cancer.'

Several preclinical investigations of an 11-nucleotide T-oligo sequence were conducted by scientists at Boston University School of Medicine, where the T-oligo technology was discovered. In vitro studies demonstrated that this T-oligo induced apoptosis in several established human melanoma cell lines without causing apoptosis in normal melanocytes, even at high T-oligo concentrations. In additional studies, the T-oligo was administered to mice with established melanoma tumours, either directly to the tumour or intraperitoneally. The growth of these tumours was reduced by 85-90% without detectable toxicity.

In a preclinical model of metastasis, when melanoma cells were exposed to the T-oligo and then injected into immuno-compromised mice, the resulting metastatic tumours were 80-85% smaller and 90-95% fewer in number than tumours in mice injected with melanoma cells not exposed to the T-oligo.

'These results reinforce what we've seen in previous studies - T-oligos appear to activate innate responses that cause the destruction of cancer cells without adversely affecting normal cells,' said Professor Barbara Gilchrest, chair of the department of dermatology at Boston University School of Medicine and chief of dermatology at Boston Medical Center, who developed the T-oligo technology. 'We are excited to advance this promising technology and continue our discovery of the underlying cellular processes that may be key to the development of novel and effective treatments for cancer.'

The T-oligo technology developed at Boston University was licensed to SemaCo. CancerVax obtained an exclusive sub-license from SemaCo in March 2004 to the T-oligo technology for use in the prevention, treatment, control, prognosis or diagnosis of cancer.

In preclinical studies, T-oligo treatment has demonstrated inhibitory effects on the proliferation of multiple tumour cell lines, including breast, ovarian, pancreatic and squamous cell carcinomas, melanoma, fibrosarcoma, osteosarcoma, and lymphoma. Administration of T-oligos has previously been shown to inhibit tumour growth in several in vivo tumour models in mice.

About T-oligonucleotides

Genetic information communicated through DNA is organised into strands called chromosomes, which end in telomeres, tandem repeats of a short nucleotide sequence several thousand base pairs long. In all mammals, the 3' strand is a repeat of TTAGGG and extends beyond the complementary strand as an overhang. This telomere overhang is tucked within the DNA to form a loop. In normal cells, disruption of this telomere loop with exposure of the TTAGGG overhang sequence appears to signal DNA damage or aging, which activates natural protective pathways to prevent excessive replication of compromised cells. In cancer cells, however, these responses are impaired, and cells with gross DNA abnormalities continue to proliferate. Telomere homologue oligonucleotides, or T-oligos, are short DNA sequences that appear to mimic telomere loop disruption. It is hypothesised that T-oligos activate natural protective pathways in the cell that cause malignant cells to stop growing and/or die.