Reengineering the immune system to kill cancer

CAR-T immunotherapy, a treatment that harnesses the body’s immune system to attack cancer, has the potential to revolutionise the way certain cancers are treated but challenges associated with cost and complexity of these therapies have limited widespread adoption.

Now, renowned Australian embryologist and stem cell scientist Alan Trounson is hoping to change that. Trounson, Emeritus Professor, Monash University and Distinguished Scientist, Hudson Institute of Medical Research is the founding CEO/President of the start-up company Cartherics.

An Australian company formed through a partnership between Monash University, Hudson Institute of Medical Research and Monash Health, Cartherics uses CRISPR to genetically reprogram a patient’s immune cells to identify and attack cancer cells. The company has filed a patent on its off-the-shelf CAR T-cell immunotherapy.

In early 2018, CAR T-Cell immunotherapy was named as the Advance of the Year by the American Society of Oncology. It works wonders for some patients, but personalised treatments are prohibitively expensive, costing up to US$450,000 per patient. Cartherics has an ambitious plan to reduce this cost tenfold.

To learn more about the company’s plans, we interviewed founding CEO and President Alan Trounson.

What is your current focus and what are your plans for the next 12–18 months?

Cartherics is building on a strong foundation of basic stem cell and immunology research, both of which have been very strong in our research institutions in Melbourne. Before I left to spend 7 years as the President of the California Institute for Regenerative Medicine (US$3 billion stem cell driver), Professor Richard Boyd and I headed the Monash Immunology and Stem Cell Labs, which focused on bringing stem cell developments into translation and clinical trials.

We decided that a merger of our independent strengths in stem cells and immunology could be focused on cancer therapies. Since we teamed up again at the start of 2016, we have been developing new technologies to better equip T cells to destroy cancer.

In the next 12–18 months, we will continue to expand and further develop our approach of using pluripotent stem cells to make very effective T cells and to protect the IP that is evolving. We hope to initiate two clinical trials as proof of concept of our CAR-T design, one in relapsed ovarian cancer and one probably in cutaneous T cell lymphomas. These will be autologous clinical trials using the patient’s own T cells. We anticipate that these studies will show safety and also perhaps have some indicators of efficacy in killing cancer in patients.

How did you come up with this technology?

The ideas for the work have evolved from our experience in immunology and clinical trials (Richard Boyd), my ideas and experience in pluripotent stem cells and translation, Ian Nesbit’s experience in commercialising discoveries in immunotherapies and Peter Hudson’s specialist knowledge in antibody design and function.

Robert Moses drew us together with his experience in managing biotechnology as a business, and many others have added their contributions — including Miles Prince, a world-leading blood cell oncologist, and Maureen Howard, ex-Stanford University and immunology project director. In the end we are a team of talented scientists and business executives developing innovative solutions. The challenge is to deliver these important therapies for eradicating cancer in a reasonable time frame and contained cost for those who need it.

What are some of the other challenges?

The challenges are everywhere. We are developing a very aggressive therapy that can wipe out kilograms of cancer in 3–4 weeks. We need to make sure that these activated T cells kill the cancer and not bystander normal cells. We are building in some sophisticated safety mechanisms with the help of international collaborators. Some risks are difficult to assess in animal models for this work because they don’t have a human immune system. However, with the numerous side effects considered and covered by our strategies, I think we should be able to efficiently rid the patient of cancer stem cells with minor side effects if any. I think funding shouldn’t be a major problem with such a desired product and approach but we are sensitive to the need of efficiency and effectiveness in the evolving studies. Since we will be using really innovative technologies there may be difficulties in getting the TGA to provide us guidance and approval for clinical trials in a timely manner. If this is a problem, we will talk to other regulators.

How do you plan to get to the market?

There is a clear pathway to market that includes the need to undertake phase II, III clinical trials, and I. We anticipate beginning some autologous clinical trials here in Australia and if these are encouraging, I expect the rights will be sold to large biotech or pharma companies who already have autologous trials underway or who want to move into this area. We will continue to develop the ‘off-the-shelf’ or allogeneic products using stem cells and gene editing. We will develop all the documentation needed by the regulator for clinical trials approval. We expect a lot of interest in this approach and will either develop the product in gastric and ovarian cancer ourselves with investor support, or partner with someone to co-develop this therapeutic approach.

What is the competition like? How are you planning to fight it?

No, we are prepared to work with others to accelerate the studies and the clinical trials. There are many potential partners and competitors but a variety of approaches are always best because it is not always predictable what might not work or work differently as a therapy in different people.

We think there is a strong national body of immune scientists and innovative clinicians here in Australia and there are many international scientists and organisations that want to help us. Eventually the most cost-effective methods will evolve into clinical use. We think our approach is very likely to be one of them. Joining great scientists together is very inspiring and we know how to get them interested. I don’t think fighting them is very productive.

How are the fields of immunotherapy and biotech evolving?

Immunotherapy has been evolving for more than 30 years. We have vaccines that will work extremely well. Gardasil is preventing human papillomavirus from causing cervical cancer. Antibodies to T cell checkpoint inhibitors are working incredibly well in some patients. This effectively removes the brakes on the T cells that hold them under control and preventing autoimmunity.

The CAR-T appear to be the front line in destroying cancer, presently most effectively in blood cancers. The world of medicine will change, in that a person’s own immune system — enhanced with smart molecular and genetic technologies — will be used to not only target cancers but also infections and autoimmunity.

We need a vital biotech industry to assist us take discovery to the clinic. Presently, we have too many virtual companies without scientists, and academic translation programs without industry participants. It is time we changed this. In this regard, Cartherics is showing the way for many others to follow. We hope our example will help build the early med-biotech industry that we have wanted for so long.

Image credit: ©stock.adobe.com/au/vitanovski