It’s been nearly 50 years since U.S. President Richard Nixon declared war on cancer. Since then, some battles have been won, others lost. But the traditional weaponry – chemotherapy and radiation – while refined and improved, is still carrying the brunt of battle duty.
In recent years, these two warhorses have been joined by a powerful new weapon. The most promising new approach to treat cancer to emerge, immunotherapy, enlists the patients’ own immune systems to fight their cancer. It’s an exciting field, with new therapeutic approaches being rapidly developed.
BioCanRx was created to build on these discoveries and approaches, to help them reach the clinic, where they can save lives as quickly as possible. In Toronto, for instance, Dr. Pamela Ohashi of the Princess Margaret Cancer Centre has developed a novel method of taking tumour-infiltrating lymphocytes (TILs), a form of T-cells, from patients, growing them in the lab with dendritic cells, another kind of immune cell, and returning them to the patient, where they can attack ovarian cancer tumours. Now, the world’s first clinical trial to use this type of adoptive cell therapy, as it is known, for ovarian cancer is giving women who are no longer responsive to conventional treatment another option.
But there still remain challenges to the widespread implementation of immunotherapy. It is now clear that even within a single patient, cancer is a genetically complex and heterogeneous disease. Its ability to evolve during therapy coupled with its propensity to shroud itself with an immunosuppressive cloak makes metastatic or widespread cancers essentially incurable with the current therapies available to the oncologist. However, our immune systems have the “potential” to evolve in lock-step with the cancer and recognize novel tumor specific antigens as they appear during progression from a normal cell to a malignant cancer. Strategies need to be developed to exploit the ability of our immune systems to recognize foreign cancer antigens while at the same time finding ways to overcome the barriers that tumours set up to block immune cell activity.
Scientists within the BioCanRx Network believe that it is not sufficient to attack each of these barriers on its own. Our approach is to develop novel combination strategies creating a multi-faceted attack on cancer to enable immune recognition and destruction of tumours wherever they hide in the body.
That’s why, today, we are focusing our funding on exactly that – research into combination therapies that together are stronger than the sum of their parts. For example:
• Dr. Julian Lum and his colleagues at the BC Cancer Agency are combining radioactive drugs with checkpoint inhibitors so that the immune response generated by the radiation can better infiltrate the cancer tumour. Their work could provide a new treatment option for metastatic prostate cancer that has become resistant to hormone therapy.
• Dr. Marcus Butler of the Princess Margaret Cancer Centre is conducting the world’s first clinical trial combining an oncolytic vaccine with checkpoint inhibitor antibodies for cancer treatment. The vaccine he is using was developed in Canada and its testing remains exclusive to Canada, as, likely, will its commercialization. The trial will involve patients with advanced solid tumours who already show an anti-cancer immune response and have not responded to conventional therapies. The combination of oncolytic vaccines with checkpoint inhibitors is one of the most exciting prospects in oncology, according to Dr. Stephen Russell of the Mayo Clinic and a member of the BioCanRx Research Management Committee.
• Dr. Yonghong Wan of McMaster University is also using an oncolytic vaccine, this time with adoptive cell therapy, to target cancers already showing an immune response. This exciting combination of therapies has a clear mechanism for working together to kill cancer cells.
This is a key example of the critical role that BioCanRx is playing in the immunotherapy field. Pharmaceutical companies, very justifiably, are focused on developing their own agents. Combining these agents with those of other companies, if it happens at all, generally happens quite a bit later in the process. The development of new therapies as single agents in a “siloed” approach is slow, expensive, ineffective and unlikely to make the rapid progress cancer patients need. We at BioCanRx are investing our funds to make these combinations happen sooner.
The other thing we’ve learned is that we need a better way to select those patients who will benefit most from these promising, but expensive, therapies. The pace that research advances today is so quick that we are missing opportunities to capture the data that results, in particular, from clinical trials. BioCanRx is capturing that data and using it to learn how to best identify those patients who will benefit from specific immunotherapy approaches. This helps to speed up the product development process and ensure that decision-making is strongly rooted in the best possible evidence.
With our funding, we are also helping to develop the foundations and infrastructure to support future immunotherapy discoveries:
• Drs. Jonathan Bramson and Raja Ghosh from McMaster University are developing a “bioreactor in a box” to enable the production of T-cells for immunotherapy in a closed system that more closely mimics the body’s production of T-cells, while reducing the costs, lab space and human resources required for current methods of producing T-cells for immunotherapy. Their work will ensure that the high cost of producing the needed immune-system cells is no longer a barrier for providing immunotherapy in the clinic.
• Drs. Manoj Lalu and Dean Fergusson of the Ottawa Hospital Research Institute are leading a multidisciplinary team in developing a template for evaluating future therapeutics and designing clinical trials that are feasible, safe, effective and economical. The team will address issues that most first-in-human/early phase trials encounter and offer a structured method to evaluate available data and design an evidence-informed trial protocol, beginning with CAR-T cell therapy for blood cancers.
• Dr. Rob Holt is working with a team at the BC Cancer Agency and Ottawa Hospital Research Institute to build the manufacturing capacity to enable CAR-T therapy in Canada. This will bring this necessary, effective and highly publicized therapy to cancer patients for whom conventional treatment has not worked and who are in dire need of a new approach.
The result of our investments is the rapid testing and introduction into the clinic of combination therapies targeted to the patients who will benefit most from them, so that cancer becomes part of their past and not their present. In doing so, we are contributing to a huge improvement in quality of life of people with cancer, lowering healthcare costs by delivering the most effective therapy first and reducing the social and economic toll of this too-often fatal disease.
About the Author
Dr. John Bell is Sr. Scientist, Centre for Innovative Cancer Research, Ottawa Hospital Research Institute; Professor, Departments of Medicine and Biochemistry, Microbiology & Immunology, University of Ottawa and Scientific Director, BioCanRx- Biotherapeutics for Cancer Treatment.