Enabling a dramatically different approach to cancer therapy
It is well established that some bacteria are more damaging to tumours than they are to healthy human cells. These microbes hold great promise for cancer treatment. They kill cells in a way that can potentially synergise with radiotherapy or chemotherapy, and they can recruit the patient’s own immune system to fight back.
Excitingly, these microbes can also be enhanced by “arming” them with genes that sensitise the cancer to prodrugs – compounds that become highly effective anti-cancer drugs when activated in the tumour.
However, the road toward utilising these microbes as a therapeutic measure is fraught with difficulty. There are many issues associated with administering potentially disease-causing agents to people who are already sick.
A major problem is how to keep track of these microbes in patients; i.e. how to determine whether a microbe is only infecting the tumour, and not damaging healthy tissue. Existing technology has no answer, short of collecting biopsies of tissue from multiple organ sites and measuring the levels of microbes present in each – an approach that would not be practical or ethical.
With Cancer Research Trust NZ support, Dr David Ackerley and his Microbial Biotechnology team at Victoria University have been working closely with Dr Jeff Smaill’s Medicinal Chemistry group and Dr Adam Patterson’s Translational Therapeutics team at the Auckland Cancer Society Research Centre from the University of Auckland. Together, their primary goal has been to develop novel enzymes, prodrugs and other molecules to advance microbial cancer therapies into the clinic.
Their major breakthrough has been the discovery that some of the bacteria-derived enzymes that activate prodrugs to improve cancer cell killing can also activate a range of molecules used in PET (positron emission tomography) scans. This provides a means for using standard hospital PET scanning equipment to image the tissues that contain genetically-armed microbes.
Using this technology it should ultimately be possible to image a patient in a whole-body PET scan to establish that the therapeutic microbes are only infecting tumours and then administer a suitable dose of prodrug to enhance killing of tumour cells. This will improve the efficacy of microbial anti-cancer therapies and minimise the safety concerns that currently stand between these therapies and widespread clinical use.
The New Zealand team is now looking to collaborate with researchers at the University of Nottingham and the MAASTRO Radiation Oncology Clinic in the Netherlands, to conduct advanced preclinical and clinical trials.