Up until now, individuals diagnosed with cancer have had to endure long, complex, and sometimes painful treatments. The new cancer therapeutic Verotoxin (VT-1) gives patients hope to put an end to these burdensome treatments.
Recently, the University of Toronto Innovations Foundation (UTIF), U of T’s commercialization office, has entered into an agreement with LISI Therapeutics Inc., granting LISI sole rights to the patented technology – the use of Verotoxin (VT-1) in cancer treatment.
A breakthrough cancer treatment discovered by Dr. Hannah Farkas-Himsley, University of Toronto; Dr. Cliff Lingwood, The Hospital for Sick Children; and Dr. Richard Hill, University Health Network, VT-1 is a member of the family of Shiga toxins that targets cancer cells through its dual action, binding and selectively killing cancer cells.
This therapeutic is a novel step forward for cancer research, in that it particularly targets drug resistant cancer tumours. In addition, the treatment potentially has multiple sites of action: the tumour itself, and the tumour blood vessels that provide nutrients to the tumour.
Targeting tumour blood vessels (anti angiogenesis) is a more recent approach to the treatment of neoplasia. Thus, VT-1 has antineoplastic and potential antiangiogenic activity, which in combination, make a powerful new approach to cancer treatment.
The way the treatment works is that VT-1 targets CD77 (a glycolipid) expressed on the cell surface of certain types of cancer, including astrocytomas (glioblastoma), ovarian cancer, breast cancer, testicular cancer, and certain lymphomas. Preliminary studies have suggested that CD77 may also be present on additional tumor types.
Increased expression of the receptor is also noted in metastases and cancers that become resistant to conventional treatments, such as Multiple Drug Resistant (MDR) tumours. Research using VT-1 to treat MDR tumour cells has demonstrated significantly increased anti-tumour effect on these cancers, which has gained interest in the medical oncology community into the potential use in patients with MDR tumours. This suggests that such MDR cancers may be particularly attractive candidates for this targeted toxin therapeutic approach.
The reason for tumour cell CD77 expression is unknown, but its increase in drug resistant cancers is due to a role for the MDR protein in CD77 synthesis. As the MDR protein pumps toxic drugs out of the cancer cells to make them resistant, it makes more CD77, and hence, becomes more sensitive to VT-1 – a ‘Catch-22’ scenario! The appearance of CD77 on these tumour tissues, and lack of expression on most normal human tissues offer an opportunity for targeted cancer therapy.
To administer this treatment, VT-1 will be directly injected into the tumour at the time of surgery to remove the tumour. Most of the tumour will be removed, but the residue that cannot be reached will be targeted and injected with VT-1.
Before a patient can be treated with VT-1, CD77 expression by the tumour must be confirmed, as the treatment only works via the CD77 receptor.
VT-1 is naturally expressed in a certain strain of bacterium known as E. coli 0157:H7. Infection with E. coli O157 H7 can cause kidney damage in young children, but adults are largely resistant. The VT-1 dosage proposed in the cancer treatment is below that determined to cause any adverse effects in animals.
Pilot scale quantities of VT-1 have been produced through recombinant fermentation methodologies under cGMP guidelines. Reproduced via a well-characterized and standardized E. coli vector, VT-1 can be manufactured inexpensively through traditional, industry-proven fermentation techniques producing high yields of product. Continued development of fermentation processes may result in enhanced yields reducing production costs even further.
The first paper on this VT-1 as a potential cancer treatment was written in 1995. Since this time, the treatment has eliminated human glioblastoma brain tumours in mice. With only one injection, the tumours disappeared after five – 12 days.
LISI Therapeutics Inc. is an Ontario-based biotechnology research and development company founded to develop therapeutic entities for cancer and other life-threatening illnesses. LISI seeks to in-license technologies, such as VT-1, which are at late stage pre-clinical development status, and add value through clinical development programs. Clinical trials for VT-1 cancer treatment are in the planning stages.