Empirical observations over the past many decades have suggested that certain types of virus infections could lead to cancer regression.
However, the use of so-called oncolytic viruses (OV) with the intent to treat cancer had been met with skepticism. Now, thanks to technological advancements in genetic engineering and virus manufacturing, oncolytic virotherapy has gained considerable attention and demonstrated significant, though perhaps limited, clinical successes.
The Centre for Drug Research and Development (CDRD) have been working on ways to potentiate the utility of OV for cancer therapy in the hope that one day these strategies may be able to eliminate, or at the very least significantly reduce the need for traditional cytotoxic chemotherapy. Reducing the use of toxic treatments that impair the patient’s immune system is expected to lead to better overall survival and quality of life for countless cancer patients.
Dr. Ismael Samudio, Head of Biologics at CDRD, has been preoccupied on how best to translate OV strategies to the clinic, and in particular how to make these viruses work better in combination with targeted agents regardless of whether they are small molecules or antibodies. As Samudio explains, “We are cognizant that such a thing as a magic bullet for cancer is unlikely to exist. Pre-empting that, our work on oncolytic viruses is really trying to find the tools that we could take to the clinic (small molecules, antibodies) to make these agents successful in more cancer patients.”
OV are a very powerful way to combat cancer. They are mostly genetically engineered to specifically target and kill cancer cells, without having an adverse reaction to the patient. They are also known for inducing an immune response against the cells they infiltrate.
Currently, CDRD is working with two distinct types of OV. One of them is the precursor of Maraba – a potent engineered virus currently in clinical trials. The Centre is not aiming to treat one particular type of cancer and hopes that their research will effectively work in multiple tumour types.
“Tumour cells, in general, have defective antiviral responses, and that’s why oncolytic viruses preferentially infect them,” says Samudio. “Cancer cells do not like to stop making proteins. They’re constantly growing and constantly making proteins. Normal cells have mechanisms that stop uncontrolled growth and protein synthesis. Because those mechanisms are defective in cancer cells, viruses infect them and they don’t have a way to shut down the production of the virus, resulting in massive viral expression and death of the infected tumour cells. Some cancer cells are more sensitive than others to OV, and understanding how to improve the efficacy or these biological agents is paramount to their success in the clinic.”
The Centre so far has seen successful infection in every single cancer line that they have tested. Some cancer cells, however, tend to be able to escape death induced by the OV, and thus in collaboration with several researchers, CDRD is developing strategies to increase infectivity and engagement of the immune system.
“With some of these strategies, we don’t expect that there’s going to be infection of normal tissue” comments Samudio. “Nonetheless, we remain focused on delivering the treatment to where it needs to go – the tumour. There is no reason if your heart is healthy, or your kidney or liver, to expose those organs to our chemo-biological interventions – whether small molecules or antibodies – and reduce the safety of our approach. We want to make sure that those interventions go to the tumour tissue.”
CDRD expects for some of these efforts to take at least ten years to reach the clinic. Drug development can be a very daunting process, and of course, scientists and clinicians want to make sure it passes all safety and efficacy standards. CDRD is a unique organization that focuses on a number of therapeutic areas, including cancer, auto-immune diseases, infectious diseases, neurodegenerative diseases and neurobiology in general. The knowledge gained at the Centre through innovative approaches, outside-the-box thinking, and cross-pollination of disciplines will ultimately lead to life-saving therapies.
“Oncolytic viruses are such an amazing tool. They can, directly and indirectly, inhibit cancer progression, and I expect them to eventually become a mainstay in cancer therapy”, adds Samudio.
