Naoto Hirano, PhD, MD

Senior Scientist, Princess Margaret Cancer Centre
Keywords: immunotherapy, adoptive cell therapy, T cell responses, T cell activation, lymphocytes

My research focuses on developing new immunotherapies that use a patient’s own immune system to recognize and destroy cancer cells. I am especially interested in T cells, a type of white blood cell that can be trained or engineered to find cancer with great precision. Over my career, I have worked to understand how T cells recognize abnormal cells and how we can redesign these responses to create safer, more effective cancer treatments. At Princess Margaret Cancer Centre, my team develops next-generation cellular immunotherapies, including engineered T cells (TCR-T and CAR-T cells) and bispecific T-cell engagers. We have created several technologies now used internationally, such as tools to identify the best T-cell receptors for therapy and a new signaling system (called JAK–STAT CARs) that can improve T-cell function. These innovations have led to multiple patents, partnerships with biotechnology companies, and new clinical trials. Our group launched Canada’s first T-cell receptor gene therapy program and helped initiate the first-in-human clinical trial of a JAK–STAT CAR-T therapy at Princess Margaret. This trial demonstrated a promising safety profile and early signs of antitumor activity, showing that discoveries made in our laboratory can translate into meaningful treatments for patients. Training the next generation of immunotherapy researchers is also a central part of my work. I have mentored more than 40 trainees, many of whom now lead research programs or clinical services in Canada and internationally. Through leadership roles at Princess Margaret, the Centre for Immunology to Immunotherapy, and the University of Toronto, I work to build collaborative environments that accelerate discovery and bring new therapies to patients faster. Ultimately, my goal is to create immune-based treatments that work for all patients, regardless of genetic background. By overcoming barriers such as HLA polymorphism and developing universal T-cell therapies, I aim to expand access to life-changing immunotherapies for individuals with cancers that currently have limited treatment options.

Enhancing a patient’s own T cells to eliminate blood cancer

Study Status: Active
Study Purpose: To boost the natural cancer-killing ability of T cells against blood cancer.
Background: T cells of the immune system are able to attach to cancer cells and kill them. It is difficult to identify targets that are on cancer cells and not on healthy cells, or else the T cells will target and kill the healthy cells as well. Once a target is identified, special receptors can be designed on the T cell to attach to the target. Blood cancers have a target that is called CD19. This target has been used for many years and has been very successful as a treatment option. Unfortunately, over time these T cells gradually become less effective in killing the cancer cells. The Hirano lab has devised a way to boost the anti-cancer effectiveness of the T cells in patients with blood cancer that has CD19.
Study Methods: The study is set up to target various CD19 blood cancers and will evaluate the safety and efficacy of the T cells designed to target CD19. The study started in July 2023 and is currently recruiting participants.
Health Conditions: Blood disorders,Cancer

 

Rare T cell receptor identification

Study Status: Completed
Study Purpose: To identify T cell receptors that recognize an individual’s particular cancer. Once these receptors are identified, they can be used to treat the disease.
Background: T cells are part of the immune system. They are a major part of keeping the body healthy. A cancer cell produces proteins that are not usually found in healthy cells. These proteins are cut into pieces and put on the surface of the cancer cell. T cells are able to recognize these pieces through their T cell receptors. T cells then attach to the cancer cell and are able to kill them. So, in order for the immune system to kill the cancer cell, a T cell with the correct T cell receptor needs to come close enough to the cancer cell to find it, attach to it, and kill it. If we knew what T cell receptor is able to attach to the cancer in a patient, then we could use this receptor to kill the cancer. This treatment option has been around for a while now and it can be very effective at fighting cancer. However, one major challenge is finding the correct T cell receptors. The Hirano lab has generated a procedure that is able to find the T cell receptors that can bind to a patients’ cancer.
Study Methods: Knowing a patient’s cancer type and genetic background, their T cells can be rapidly scanned to find receptors that can bind their cancer. Once these receptors are identified, they can be used to fight the cancer.
Key Findings: The Hirano method is able to discover T cell receptors that are difficult to find using traditional methods, since the Hirano method has a much higher sensitivity. A company (TCRyption) was formed at UHN to further develop a large-scale platform for the technology. TCRyption was acquired by Treadwell Therapeutics. This allows for efficient T cell receptor scanning for large groups of patients.
Health Conditions: Cancer

 

For a list of Dr. Hirano's publications, please visit PubMed or Scopus.
Senior Scientist, Princess Margaret Cancer Centre
Tier 1 Canada Research Chair in Immunology to Immunotherapy
Chair, Immuno-Oncology Program, Princess Margaret Cancer Centre
Associate Director for Research, Tumor Immunotherapy Program, Princess Margaret Cancer Centre
Co-Chair, Center for Immunology to Immunotherapy (Ci2i), University Health Network
Network Investigator, BioCanRx