UofTMed Research Reflections: On FDA Approval of a New “Living Drug” for Cancer

Sep 5, 2017
Linda Quattrin

Naoto HiranoPrecision medicine took a big step forward last week as the U.S. FDA approved a new form of immunotherapy for cancer: anti-CD19 chimeric antigen receptors – or CAR-T cells – for the treatment of a deadly form of childhood leukemia, known as acute lymphoblastic leukemia. U of T Med’s Linda Quattrin discussed this development with hematologist and oncologist Naoto Hirano, Associate Professor of Medicine, Department of Immunology at U of T, and Senior Scientist at Princess Margaret Cancer Centre, UHN. Professor Hirano’s research focuses on cancer immunotherapy, especially adoptive T cell therapy.

CAR-T cell therapy involves engineering a cancer patient’s own immune cells to turn them into weapons against their specific tumour cells. How does that work?

A patient’s own T cells are isolated from the peripheral blood and engineered with the CAR gene targeting a cancer antigen. The gene-engineered T cells are then expanded and infused back to the patient after chemotherapy is given to make space and remove immunosuppressive mechanisms in the body. The new CAR-T cells can then specifically wipe out any remaining tumour cells, therefore improving the odds of preventing a recurrence of cancer in the future.

What are the major benefits over traditional cancer therapies and what are the potential drawbacks?

CAR-T cells or any T cell grafts used in adoptive T cell therapy are “living drugs,” which can grow and persist in the body for years. Immunotherapy can be very effective but also can be associated with a different set of adverse events that have not been seen with traditional cancer therapies. Our work in immunotherapy research is to maximize the therapeutic benefit for the patient while minimizing any potential adverse or off-target effects.

Immune therapies for cancer seem to have taken off in recent years. Tell us about the clinical trials you’re involved with in Toronto.

At Princess Margaret, the Tumor Immunotherapy Program (TIP) is involved in immune therapies for cancer. We are conducting various kinds of immune therapy clinical trials including adoptive T cell therapy, immune checkpoint blockade, small molecules and others. I am involved in the clinical trials of adoptive T cell therapy using gene-engineered T cells. In September 2016, Professor Marcus Butler (Department of Immunology) and I started a first-in-Canada T cell receptor gene therapy clinical trial at Princess Margaret in collaboration with our industrial partner, Takara Bio.  

Professor Hirano, you came from the Dana-Farber Cancer Institute at Harvard. Why was the Faculty of Medicine at University of Toronto a good move for you?

Toronto was known to be strong in basic immunology research.  By joining the group here in Toronto and using my expertise in cancer immunology and immunotherapy, I thought that we could build strong program in immunotherapy at Princess Margaret. I am happy to say that we have built a great program that bridges great science to important clinical treatments that are new and promising. 

Finally, what should we watch for next as immune therapies continue to move into the clinic?

Anti-CD19 CAR therapy is the first gene therapy for cancer approved in North America. It is exceptional in that the treatment is effective in the majority of patients who receive it. However, many of the other immune therapies are effective only in a subset of patients with some types of cancer. We investigators need to develop immune therapies that can benefit all Canadians with cancer.


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