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Immune Therapy Program
Princess Margaret Cancer Centre
One of the top 5 cancer research
centres in the world.
Leading the way with the most
comprehensive Immune Therapy
program in Canada.
Leading the Way in Immune Therapy for Cancer
Overview
The Immune Therapy Program at the Princess Margaret Cancer Centre draws from the basic
science and clinical strengths of one of the top 5 cancer research centres in the world. Led by
an award-winning team of researchers and physicians, The Princess Margaret is positioned to
become one of the global leaders in Immune Therapy for cancer treatment. This program is the
most comprehensive Immune Therapy Program in Canada.
This report provides an overview of our program and addresses the following:

Section I: The Immune System and Cancer (Page 3)
To appreciate the power of Immune Therapy, it is important to begin by understanding the
immune system itself and the relationship between cancer and the immune system.

Section II: What is Immune Therapy? (Page 6)
Immune Therapy is based on the principle of using the body’s own immune system to combat
disease. Immune Therapy is not just one type of treatment; it includes a variety of strategies.

Section III: Immune Therapy at The Princess Margaret (Page 7)
The Princess Margaret has invested in the development of a broad spectrum of Immune Therapy
treatments in order to benefit the widest range of patients. This section discusses a few
examples of the top quality care we deliver to our patients by translating the science of cancer
and immunology into practice.

Section IV: What is the future of Immune Therapy? (Page 14)
There is enormous momentum in the field of Immune Therapy. Supporting our Immune Therapy
Program will ensure that our patients continue to benefit from leading-edge breakthroughs.

Section V: Why is The Princess Margaret positioned for success? (Page 15)
The success of the Immune Therapy Program is due to our deep knowledge base and cuttingedge expertise in clinical trials, as well as valuable partnerships with external centres.
Section VI: Who are the leaders in Immune Therapy? (Page 16)
Our award-winning team of researchers and clinicians are leading contributors to the field of
Immune Therapy.
The Princess Margaret strategically supports different areas of cancer research such as
Immune Therapy in order to provide patients with access to state-of-the-art therapies. We
believe that the best clinical treatments for curing cancer will be achieved by combining different
cancer treatments.
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Section I: The Immune System and Cancer
What is the immune system?
In order to understand the power of Immune Therapy for cancer, it is helpful to know how the
immune system works.
The immune system exists to protect our bodies from disease-causing germs, such as viruses
and bacteria. This complex and remarkable defense network can be broken into two
categories: the innate immune system and the adaptive immune system (shown in Figure 1).
Each system is made up of different types of cells and molecules. The innate immune system is
important as a “first line of defense” against germs. It plays an important role by alerting and
initiating the adaptive immune response. However, this first line of defense does not provide
long-lasting protection against foreign invaders (or organisms) or tumours.
The adaptive immune system is responsible for providing the lifelong immunity that can follow
exposure to a disease. As it is exposed to various germs, the adaptive immune system
acquires information and is able to “remember” that it has already encountered these agents so
that it can better protect our bodies from similar attacks in the future. Immune therapies for
cancer often involve the adaptive immune system because this “memory” can apply to cancer
as well as disease-causing germs. Another advantage of the adaptive immune response is that
it can specifically destroy particular “targets” (germs or cancer cells), while sparing healthy
tissues from attack.
Innate immune system:
Adaptive immune system:
“First line of defense”
“Second line” of defense
Rapid response
Slower response
Alerts the adaptive immune system
of threats
Mounts a long-lasting response
against threats
No “memory”
Development of “memory”
Figure 1. Key differences between the innate immune system and the adaptive immune
system.
One of the key players in the adaptive immune system is the T-cell. T-cells are the chief type of
immune cell that can directly attack and destroy cells that are infected with viruses. T-cells can
also attack and destroy cancer cells. There are many different sub-types of T-cells, each of
which bears their own unique T-cell receptor on their cell surface. Each T-cell receptor has the
unique ability to recognize different things. For example, some T-cell Receptors recognize parts
of viruses, some recognize parts of bacteria, and others recognize abnormalities in cancer cells.
The discovery of the T-cell receptor by Princess Margaret’s own Dr. Tak Mak provided, in many
ways, the Rosetta Stone for all subsequent work on the adaptive immune system. Dr. Mak’s
landmark discovery allowed researchers to define many critical properties of how T-cells
develop and function, which provided new ways to treat diseases including cancer.
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By continuing to invest in research like this, we can develop treatments that will have a greater
impact on cancer outcomes in the future.
What happens during an immune response?
After disease-causing germs enter the body, the immune system leaps into action to eliminate
them. T-cells are often the key players in this process, which involves a complex series of
events. Similarly, in order for T-cells to eliminate cancer cells, the following steps must occur
(depicted in Figure 2):
Step 1: Alerting T-cells to a threat. In order for T-cells to be effectively activated, a specialized
cell type in the innate immune system, the dendritic cell, needs to take a small piece of the
germ (or the cancer cell) and “display” it to T-cells. These small pieces of germs (or cancer
cells) are called antigens. The job of the T-cell receptor is to recognize specific antigens
present on the surface of dendritic cells. When a T-cell encounters its unique antigen, the T-cell
is alerted to the presence of that specific threat to the body and becomes activated.
Step 2: T-cell multiplication and attack. After T-cells are activated, they rapidly multiply in the
body so that there are many T-cells available to attack the threat. T-cells then work to destroy
the cells of the body that are infected with a germ. Once these infected cells are killed off, the
germs die along with them. In a similar way, T-cells can work to kill cancer cells.
Step 3: End of the T-cell response. Once the threat to the body is gone, excess T-cells that
participated in the immune response die off. However, some of these T-cells are converted to
“memory T-cells” and stay in the body. The next time the body is infected with that same germ,
these memory T-cells stand ready to rapidly destroy the threat. Therefore, memory T-cells can
provide durable, even permanent, protection against foreign invaders or cancer cells.
Figure 2. The main steps during an immune response against cancer.
Negative regulation: putting the “brakes” on the T-cell response. The immune system also
has the ability to limit the strength or magnitude of T-cell responses. This can be useful in some
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situations. For example, it would be harmful if T-cells that recognize healthy tissues were to
become activated and then proceed to destroy healthy tissues; in fact, this is exactly what
happens in auto-immune diseases. The body might also be harmed if there are too many T-cells
in overdrive, even after germs have been destroyed. There are many types of cells and
molecules that act to inhibit the T-cell response, just like the brakes in a car. In the case of
Immune Therapy for cancer treatment, however, these ‘brakes’ are not desirable. Part of
Immune Therapy is aimed at discovering ways to “release” these brakes, so that we can
unleash the power of T-cells to effectively destroy cancer cells.
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Section II: What is Immune Therapy?
Immune Therapy is based on the principle of using the body’s own immune system to combat
disease.
Although our bodies can attack many of the germs that we encounter, our immune system is
often unable to fight cancer by itself. Many people with healthy immune cells are still diagnosed
with cancer. Yet, it has been shown that treatments that manipulate the immune system can
assist in controlling cancer.
As described in Section I, there are many steps during an immune response and many ways
that the response can be blocked. Accordingly, a variety of strategies can be used for Immune
Therapy. For instance, growth stimulants for immune cells or agents called antibodies can be
administered to promote the growth or activity of specific immune cells. Alternatively, tumourkilling immune cells from a patient, such as T-cells, can be multiplied in the laboratory to
increase their numbers and enhance their ability to attack cancer cells. These cells can then be
given back to the patient. Vaccines are another form of Immune Therapy, in which small parts of
cancer cells are used to stimulate the immune system to attack the cancer.
T-cells attacking a cancer
cell (Source:
Mesotheliomalungs.org).
The type of strategy (or combination of strategies) that turns out
to be the most effective will depend on the type of cancer and
the individual patient. Our goal is to carefully evaluate each
patient and develop a personalized cancer treatment plan, which
would strategically include the most suitable combination
therapies. Immune Therapy can also be used in combination
with other cancer treatments such as surgery, chemotherapy or
radiation therapy. In fact, there is evidence that these
combinations may enhance the effectiveness of Immune
Therapy. For example, when certain types of chemotherapy kill
off cancer cells, this helps specialized immune cells (dendritic
cells) to engulf pieces of dead cancer cells and alert T-cells to
the threat of cancer.
Although Immune Therapy harnesses the body’s natural defense mechanisms, it can still have
side effects. For example, think of how sick you feel when you get the flu (caused by the
influenza virus). The negative side effects that you get are partially due to the virus, but are
mostly due to the power of the immune system. However, one of the key features of the immune
system is its ability to destroy specific targets, which lowers the risk of collateral damage to
healthy tissue.
Scientists are dedicated to developing treatments that take advantage of the “specificity” of the
immune system. By contrast, most of today’s chemotherapies cannot discriminate between
killing off fast-growing cancer cells versus other healthy, fast-growing cells such as blood cells.
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Section III: Immune Therapy at The Princess Margaret
The Princess Margaret Cancer Centre has invested in the development of a broad spectrum of
Immune Therapy treatments in order to benefit the widest range of patients. This section of the
report discusses a few examples of the top quality care we deliver to our patients by translating
the science of cancer into practice.
First Clinical Trial in Canada of Adoptive T-cell Therapy
Drs. Pamela Ohashi, Linh Nguyen and Marcus Butler at The Princess Margaret have
recently opened the first clinical trial in Canada using a specific kind of Immune Therapy called
“Adoptive T-cell Therapy”. This type of therapy is currently in clinical trials at select centres
around the world and has a track record of success.
In Adoptive T-cell Therapy, T-cells from a sample of the patient’s cancer are isolated in the
laboratory. T-cells that are found right inside tumours often have a “built-in” ability to kill off
cancer cells, but often are too few in number to efficiently kill the tumour. Scientists use growth
stimulants to dramatically increase the number of these anti-tumour T-cells, and then transfer
them back into the patient. The goal is, in many ways, to provide a larger army (or a larger
number of soldiers) to fight the tumour in the hopes of launching a stronger immune attack
against the patient’s cancer. This process is depicted in Figure 3.
Figure 3. The steps involved in Adoptive T-cell Therapy (Source, modified: Genetic Engineering
& Biotechnology News).
As part of the process of generating a T-cell product in the laboratory, a growth stimulant called
IL-2 is used. After the T-cells have been given back to the patient, IL-2 is also administered to
the patient to keep the T-cells growing in their body. Adoptive T-cell Therapy shows high rates
of cancer regression in centres such as the National Cancer Institute (in Bethesda, MD), MD
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Anderson Cancer Center in Texas, and the Sheba Medical Center in Israel. However, patients
often have severe side effects after receiving high doses of IL-2. To address this concern, Drs.
Ohashi, Nguyen and Butler at The Princess Margaret have been modifying this approach by
using a lower amount of administered IL-2 in a Phase II clinical trial. Adoptive T-cell Therapy
is a personalized approach, and the complex technology needed to produce T-cells for
clinical use can only be developed in comprehensive cancer centres like The Princess
Margaret.
Creating Next Generation Artificial Antigen-Presenting Cells (APCs)
In some cancers, and in some patients, the type of Adoptive T-cell Therapy described above
may not be an option. For example, some tumours may not have any T-cells in them, or the Tcells may not be “fit” enough to multiply in the laboratory. But what if we could “teach” new Tcells to attack tumour cells? As innovators in cancer care, researchers at The Princess Margaret
are working on this very idea to deliver a solution to this obstacle.
Drs. Naoto Hirano and Marcus Butler have
Adoptive T-cell Therapy
developed a biological tool called artificial
This form of Immune Therapy is based on taking
APCs. Similar to the dendritic cells described
a sample of T-cells from a cancer patient. T-cells
that are able to attack tumours are then multiplied
in Section I, these artificial APCs can “teach”
in the laboratory. They may also be manipulated
T-cells how to recognize and attack cancer
in the laboratory to improve their tumour-fighting
cells. This approach was proven by Drs.
activity. The T-cells are then given back to the
Hirano and Butler while they were at Harvard
cancer patient. Adoptive T-cell Therapy is a truly
Medical School. Once “taught”, these
personalized medicine since the T-cells are
“educated” T-cells were given to patients in a
matched to each individual patient.
clinical trial of “Adoptive T-cell Therapy”. No
drugs
were given to the patients during treatment, which meant that patients were able to avoid
additional
hospitalization and instead, could be treated safely as outpatients.
Drs. Hirano and Butler have brought their expertise to The Princess Margaret to create new
and more potent cancer-targeting T-cells that have been “educated” by specialized artificial
APCs. Their first generation of artificial APCs took over five years to develop due to the novelty
of the process. With a deeper knowledge base as a result of that earlier work, they anticipate
that the second generation of artificial APCs created at The Princess Margaret will only take
approximately one year. They are also developing strategies to genetically modify T-cells to
help them become tumour-attacking T-cells.
Leaders in Treatment Using “Checkpoint Blockade”
What is Checkpoint Blockade?
The immune system has developed important ways to control or regulate the immune response,
so that it is strong enough to rid the body of invaders without harming normal tissues. At a
certain point during an immune response, specific molecular switches are engaged to act like
“brakes” to slow down or stop the immune response. The points at which the brakes are applied
are called “checkpoints”. Another type of cancer Immune Therapy blocks these checkpoints.
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This releases the brakes and gives a “go” signal so that T-cells can continue to effectively attack
the cancer until it is completely gone.
This approach is known as “checkpoint blockade” and has been tested
with impressive results as a form of treatment for certain cancers. Worldleading researchers at The Princess Margaret are at the frontier of this
approach. In addition to using checkpoint blockade as part of standard
treatment at The Princess Margaret, there are a large number of clinical
trials for multiple types of cancer being conducted to investigate
improvements in the field of checkpoint blockade.
Blocking the CTLA-4 molecule
One major molecule that acts as a brake on the
immune response is called CTLA-4. Researchers
have found a way to block the function of CTLA-4,
using a monoclonal antibody. Ipilimumab* is a
monoclonal antibody drug that specifically blocks
CTLA-4. Thus, ipilimumab acts to “release the brakes”
and allows cancer-fighting immune responses to keep
going. Dr. David Hogg, Medical Oncologist at The
Princess Margaret, co-authored a major paper
describing the Phase III clinical trial using ipilimumab
that has allowed this approach to move forward into
standard clinical practice.
Monoclonal Antibodies
Antibodies are molecules that are made in
the body by a specific type of immune cell
called a “B-cell”. Antibodies are able to
bind to other molecules. Each monoclonal
antibody has a unique structure and thus
has the remarkable ability to recognize and
bind only to its specific corresponding
“target” molecule.
Some monoclonal antibodies are used to
target and kill certain types of cancers of
the blood (lymphoma) or breast cancer;
others are used to “release the brakes” on
the cancer-fighting immune response.
Ipilimumab is acknowledged as the first and only
*The suffix “-mab” is used to indicate that a
treatment clinically proven to extend the lives of
drug is a monoclonal antibody.
melanoma patients. Currently, however, the cost of
ipilimumab is only covered if it is given as the “second line” of treatment for patients. Medical
Oncologist Dr. Anthony Joshua and Senior Scientist Dr. Pamela Ohashi are studying
ipilimumab in a clinical trial as a “first line” treatment for patients to help improve the standard of
care and further understand which patients would benefit the most from this drug.
Medical Oncologist Dr. Marcus Butler was involved with some of the very first ipilimumab Phase
I clinical trials. He is about to open a clinical trial testing ipilimumab versus a class of drugs
known as “interferon”, given to patients after their surgery with the aim of preventing the cancer
from coming back. In addition, Dr. Naoto Hirano, Scientist at The Princess Margaret, has a
track record of success in developing treatments using ipilimumab in combination with Adoptive
T-cell Therapy for metastatic melanoma. Researchers at The Princess Margaret are also
studying the effects of ipilimumab as a way of treating cervical cancer.
Blocking the PD-1 molecule
PD-1 is another molecule that acts as a “brake” on the immune response. T-cells will display
PD-1 on their surfaces under different circumstances. Because of this, there are many ways to
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influence the function of T-cells when patients are treated with agents that block PD-1. One
particular way is at the site of the tumour.
What happens is that, when T-cells with PD-1 molecules on their surface enter a tumour, cancer
cells trigger the PD-1 molecule causing the T-cells to shut off. Therefore, even though there are
T-cells in the tumour that are capable of recognizing and killing cancer cells, they are
“paralyzed” on the spot.
This process is depicted in Figure 4:
T-cells receive signals to migrate into the tumour.
Cancer cells protect themselves by making a
molecule on their surfaces called PD-L1.
The PD-L1 molecule on the cancer cells engages
PD-1 on the T-cells.
The T-cells are shut off and cannot destroy the
cancer cells.
Figure 4. Flow chart illustrating how the PD-1 molecule acts as a “checkpoint” molecule,
blocking the immune response against cancer cells.
In order to prevent the shutdown of the T-cell response, various monoclonal antibodies that
disrupt PD-1 activity have been developed. While Immune Therapy is already considered a
targeted treatment, blocking PD-1 is even more specific because it selectively targets the
immune cells that are attacking the tumour. As a result, strategies based on blocking PD-1
have demonstrated a high rate of tumour regression with a low rate of side effects.
One example of a PD-1 monoclonal antibody that Drs. Anthony Joshua and David Hogg are
studying is nivolumab. It has shown promising results in lung cancer, one of the deadliest types
of cancer. Dr. Joshua has also co-authored an important paper describing another PD-1
blocking drug called MK-3475, which was given to patients with metastatic melanoma. Together
with Medical Oncologist Dr. Natasha Leighl, Dr. Joshua has opened a Phase I clinical trial
studying the effects of MK-3475 in lung cancer patients. Dr. Marcus Butler is preparing to open
a clinical trial investigating a PD-1-blocking drug known as MEDI4736 in melanoma patients, as
well as another clinical trial studying the effects of the same drug in patients with melanoma,
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uveal melanoma, lung cancer, liver cancer, pancreatic cancer, triple negative breast cancer,
head and neck cancer and gastroesophogeal cancer.
Moving Towards Personalized Immune Therapy and Combination Therapies
With the recent surge of new types of Immune Therapies, it will be important to evaluate and
determine which therapies are appropriate for each individual patient. Because each person is
unique and each cancer also develops in a unique way, we expect that successful Immune
Therapy strategies will have to be tailored to each person. The Personalized Cancer Medicine
platform at The Princess Margaret includes finding targeted treatments for each individual
patient. Our researchers are committed to defining a road map that will reveal the optimal
strategies for each patient. In order to do this, we must begin to compare different therapies and
determine which combinations of therapies work best together. Dr. Marcus Butler will open a
clinical trial comparing a PD-1-blocking drug (MK-3475) versus a CTLA-4-blocking drug
(ipilimumab) in patients with metastatic melanoma. In a Phase III clinical trial for metastatic
melanoma, Dr. David Hogg is investigating the effects of the PD-1-blocking drug nivolumab as
a treatment alone and as a treatment in combination with ipilimumab. The purpose of this study
is to investigate whether these approaches will extend survival in certain patients compared to
treatment with ipilimumab alone. Similarly, Medical Oncologist Dr. Lillian Siu, the Co-Director
of the Robert & Maggie Bras and Family New Drug Development Program at The Princess
Margaret, has opened a Phase I clinical trial studying nivolumab as a treatment alone and in
combination with ipilimumab in patients with renal cancer.
Cancer Vaccines
The goal of cancer vaccines is to alert T-cells to the presence of cancer and to initiate a strong
T-cell response against the tumour. There are different ways that this can be achieved.
Dr. Amit Oza, Medical Director of the Cancer Clinical Research Unit at The Princess Margaret,
is leading a clinical trial using the vaccine DPX-Survivac for the treatment of ovarian cancer.
The design of this trial draws upon Dr. Oza’s expertise as Co-Chair of the Gynecology Site
Committee of the NCIC Clinical Trials Group and as a member of the Gynecologic Cancer
InterGroup.
Dr. Jeffrey Medin, Senior Scientist at The Princess Margaret, has
established the expertise to alter viruses so that they can
potentially be used as cancer vaccines. Working with Dr.
Christopher Paige, Senior Scientist and Vice President of
Research at UHN, and Medical Oncologists Drs. Mark Minden and
Andre Schuh, Dr. Medin has made viruses which secrete
Dendritic cells growing
molecules called cytokines which tip off the immune system that
in the laboratory.
cancer cells are present. A clinical trial to test this vaccine in
patients with acute myeloid leukemia is currently being designed.
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Another promising cancer vaccine strategy is to use dendritic cells (described in Section I) to
‘display’ small pieces of cancer cells (called antigens) in order to effectively activate T-cells. In
this approach, dendritic cells that display cancer antigens are made in the laboratory using a
patient’s own blood cells. The dendritic cells are then injected into the patient with the aim of
turning on a cancer-fighting immune response in the patient. The Princess Margaret is currently
building a team that will be able to produce dendritic cells from individual patients to test as a
vaccine strategy.
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Examples of Immune Therapy at The Princess Margaret: A Summary
Type of Immune
Therapy:
Investigators:
Description:
Adoptive T-cell
Therapy
Drs. Ohashi,
Nguyen, Butler
One approach of Adoptive T-cell Therapy
relies on extracting cancer-fighting Tcells from a patient’s tumour, multiplying
them in the laboratory, and then giving
them back to the patient. It is a type of
personalized medicine using T-cells that
are matched to each individual patient.
Artificial AntigenPresenting Cells
(aAPCs)
Drs. Butler,
Hirano
aAPCs can be used to “teach” a patient’s
T-cells to develop into cancer-fighting Tcells. These T-cells can then be used in a
type of Adoptive T-cell Therapy.
Checkpoint
Blockade
Drs. Butler,
Joshua, Hogg,
Ohashi, Siu
and Leighl
Checkpoint blockade uses monoclonal
antibodies to “release the brakes” on the
immune response against cancer.
Cancer Vaccines
Drs. Oza,
Medin, Paige,
Minden, Schuh
Cancer vaccines work by alerting T-cells
in the body of a cancer threat and
stimulating them to destroy cancer cells.
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Immune Monitoring Laboratory
An essential component of any world-class Immune Therapy program is the establishment of an
Immune Monitoring Laboratory. Dr. Marcus Butler has established this facility at the Princess
Margaret Cancer Centre and is expanding and developing the current expertise with his
research team. By monitoring changes in the immune response to tumours in the blood and in
tumour biopsies, our researchers can begin to evaluate in detail the responses of each patient
to therapy. This process is critical in helping us understand why a given type of therapy does or
does not work, and ultimately allows us to predict which drug would be the most effective for
each individual patient.
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Section IV: What is the future of Immune Therapy?
Unprecedented momentum in Immune Therapy for Cancer Treatment
The total number of currently active clinical trials listed by the U.S. National Cancer Institute
(NCI) is over 12,000. Of these trials, 3,3741 involve experimental Immune Therapy treatments.
This means that approximately 30% of all active clinical trials currently run through the
NCI involve Immune Therapy.
Clinical trial phase:
Number of trials involving Immune
1
Therapy in each phase :
Phase I
1,047
Phase II
2,094
Phase III
443
Phase IV
67
1
As of November 20, 2013
In November 2013, the Society for Immunotherapy of Cancer (SITC) held its 28th Annual
Meeting, with a record number of 1,100 attendees. With the recent landmark achievements in
the field of Immune Therapy, and the growing number of immune-based drugs in various
phases of testing and standard medical use, Immune Therapy is poised to make a lasting
impact in the fight against cancer.
The Future of Immune Therapy at The Princess Margaret
Accelerating our advancements in immune-based therapies is a top priority for The Princess
Margaret. Recent developments in understanding the immune system, including those led by
the world-class researchers at The Princess Margaret, make this an area of great promise. As
Immune Therapy research becomes more widely studied, it is increasingly important that we
empower our team to translate leading-edge Immune Therapy discoveries to clinical patient
care as effectively as possible.
In order to maintain our position as one of the top 5 cancer research centres in the world and to
realize the full potential of our world-class Immune Therapy Program, there are specific areas
that we need to invest in:
1) Supporting novel clinical trials that use different strategies to improve the immune
response against cancer.
2) Creating teams of experts to comprehensively evaluate the immune response that
patients have against cancer. This will be critical to provide a framework to predict
which type of treatment will benefit each patient the most.
3) Supporting the development of new ideas that may lead to innovative strategies to
improve the immune response against cancer.
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Section V: Why is The Princess Margaret positioned for success?
Leading features of Immune Therapy at The Princess Margaret
 Cutting-edge research expertise spanning from basic immunology discoveries though
clinical trials of Immune Therapies.
 Established technologies to produce various types of T-cells for clinical use that can
destroy cancer cells.
 Dedicated team of researchers for detailed analysis of patients’ immune responses
against cancer.
 World-class teams to support all aspects of the development and implementation of
clinical trials.
 Access to agents sponsored by the U.S. National Cancer Institute Cancer Therapy
Evaluation Program for use in early phase clinical trials.
 Large patient population size, allowing the evaluation of Immune Therapies in many
different types of cancers and individuals.
 A specialized facility for manufacturing cell products for clinical use under “Good
Manufacturing Practices” (GMP).
 Participation in a wide variety of industry-sponsored clinical trials.
 Extensive, proven expertise in drug development and conduct of practice changing trials.
 Full repertoire of complementary modalities (chemotherapy, clinical genomics,
epigenetics) to enable rapid testing of combination therapies.
Leveraging our partnership with Immune Therapy across North America
In addition to fostering our own leading-edge researchers, the Immune Therapy Program has
forged partnerships with numerous external organizations involved in Immune Therapy. These
partnerships include:
The Cancer Immunotherapy Trials Network (CITN). The CITN is a U.S. National Cancer
Institute initiative that allows us to collaborate with member institutions and industry sponsors to
advance the progress of Immune Therapy. The Princess Margaret is the only Canadian site
in the CITN.
The Canadian Cancer Immunotherapy Consortium (CCIC). Dr. Pamela Ohashi was one of
the founding members of the CCIC, whose mission is to support the development, advancement
and promotion of cancer immunotherapy in Canada.
Surgery Branch, U.S. National Cancer Institute (NCI). The technology to produce clinical
grade cells for Adoptive T-cell Therapy at The Princess Margaret was established in
collaboration with the world-renowned Dr. Steven Rosenberg at the NCI.
The Oncology Clinical and Translational Consortium (OCTC): Princess Margaret Cancer
Centre is among the six cancer centres worldwide selected by GlaxoSmithKline (GSK)—one of
the world’s largest oncology drug companies—as a preferred centre of excellence to accelerate
translation of research into new therapies for patients. The Princess Margaret was the only
Canadian institution chosen for this important initiative. In forming the consortium GSK
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and The Princess Margaret will gain expertise in anti-cancer therapeutics including targeted
therapies and immunotherapies.
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Section VI: Who are our leaders in Immune Therapy?
Dr. Pamela Ohashi, PhD, FRSC
Director, Immune Therapy Program
Co-Director, The Campbell Family Institute for Breast Cancer Research
Senior Scientist, Princess Margaret Cancer Centre
Expertise: T-cell Activation versus Tolerance, Immune Surveillance of Cancer,
Tumour Immune Therapy
Dr. Ohashi trained in the laboratory of a Nobel Laureate in Medicine. Her laboratory at The
Princess Margaret has made key contributions to our understanding of the immune response
against healthy tissues and cancer cells. Dr. Ohashi spearheaded the establishment of the first
clinical trial in Adoptive T-cell therapy for cancer in Canada.
Dr. Ohashi has received a number of prestigious awards and honours, including the American
Association of Immunologists (AAI) Pharmingen Investigator Award, the National Cancer
Institute of Canada’s William E. Rawls Award, The Canadian Society of Immunology’s
Investigator Award, as well as a Canada Research Chair. She has also been elected as a
member of the Royal Society of Canada, and was selected to give a Distinguished Lecture at
the AAI Annual meeting.
Dr. Marcus Butler, MD
Medical Oncologist
Clinical Site Group Membership: Melanoma & Skin, Gynecologic
Before joining The Princess Margaret, Dr. Butler was an Instructor in Medicine at Harvard
Medical School and a Clinical Fellow in Medicine at the Dana-Farber Cancer Institute. His
expertise includes clinical trials in a variety of Immune Therapies including Adoptive T-cell
Therapy and Checkpoint Blockade. He is the Director of the Immune Monitoring Laboratory at
The Princess Margaret. In 2007-2008, Dr. Butler was recognized with the Dunkin’ Donuts Rising
Stars Program Award at the Dana-Farber Cancer Institute, Harvard Medical School.
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Dr. Naoto Hirano, MD, PhD
Associate Director for Research, Immune Therapy Program
Scientist, Princess Margaret Cancer Centre
Expertise: Adoptive T-cell Therapy, Human T-cell Biology
Dr. Hirano was an Assistant Professor at Harvard Medical School at the Dana-Farber Cancer
Institute before moving to The Princess Margaret. Among his contributions to the field of
Immune Therapy, he developed a human “artificial antigen-presenting cell” system that has
been used to produce cancer-fighting T-cells for Immune Therapy.
In 2009, he was awarded the American Society of Hematology Scholar Award and the Dunkin’
Donuts Rising Stars Program Award. He was recognized by the Ontario Institute for Cancer
Research with the Investigator Award in 2011.
Dr. David Hogg, MD, FRCP(C)
Medical Oncologist
Clinical Site Group Membership: Melanoma & Skin, Sarcoma
Dr. Hogg has been an attending physician in the Division of Medical Oncology since 1988. He
has been the principal investigator of many clinical trials at The Princess Margaret. Dr. Hogg
participated in the pivotal clinical trial that led to the approval of ipilimumab Immune Therapy for
metastatic melanoma.
Dr. Hogg has been the recipient of many awards including the Murray Muirhead Award, The
Issei Scholarship in Medicine and Surgery and the Chappell Prize in Clinical Medicine.
Dr. Anthony Joshua, MBBS, FRACP, PhD
Medical Oncologist
Clinical Site Group Membership: Genitourinary (GU), Melanoma & Skin,
Endocrine
Dr. Joshua co-authored a landmark study in the New England Journal of Medicine in 2013
describing a novel Immune Therapy treatment based on blocking signals that inhibit an immune
response. He has also participated in developing Immune Therapy using Tumour-Infiltrating
Lymphocytes at The Princess Margaret.
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Dr. Joshua received the 2013 Rising Star in Prostate Cancer Research from Prostate Cancer
Canada. He was also awarded the Pier Luigi Tolaini CCPC Young Investigator Award from the
Coalition to Cure Prostate Cancer in 2012.
Dr. Tak Mak, OC, PhD, DSC, FRSC, FRS
Director, The Campbell Family Institute for Breast Cancer Research
Senior Scientist, Princess Margaret Cancer Centre
Dr. Mak is one of the most cited medical researchers in the world. He discovered the T-cell
receptor, known as the “Rosetta Stone” of immunology.
Dr. Mak has won international recognition in the form of the Emil von Behring Prize, the King
Faisal Prize for Medicine, the Gairdner Foundation International Award, the Sloan Prize of the
General Motors Cancer Foundation, the Novartis Prize in Immunology and the Paul Ehrlich
Prize and Ludwig Darmstaedter Prize of Germany, among many others.
He also holds Honorary Doctoral Degrees from universities in North America and Europe, is an
Officer of the Order of Canada, and has been elected a Foreign Associate of the National
Academy of Sciences (USA), a Foreign Associate of the American Academy of Arts and
Sciences, as well as a Fellow of the Royal Society of London (UK). Dr. Mak was recently
awarded the Order of Ontario.
Dr. Jeffrey A. Medin, PhD
Senior Scientist, University Health Network (OCI, TFRI, TWRI
appointments)
Dr. Medin’s lab focuses on the development and implementation of gene therapy by integrating
viral vectors for inherited and acquired disorders. Dr. Medin heads 2 independent, multidisciplinary teams that are implementing first-in-human gene therapy trials involving lentiviral
vectors for correction of Fabry disease and to generate potent anti-cancer vaccines.
Dr. Medin has won a National Research Council Associateship Award, a USDOD Prostate
Cancer New Investigator Award, and the 2011 Distinguished Alumni Award for Achievement
from the University of Wisconsin-Parkside. Dr. Medin founded the Vector Core Facility at the
TWH.
The Princess Margaret Cancer Foundation | Page 20
Dr. Malcolm Moore, MD
Director, Bras Drug Development Program
Director, McCain Centre for Pancreatic Cancer
Medical Oncologist
Dr. Moore is Head of the Division of Medical Oncology and Hematology, Department of
Medicine at Princess Margaret Cancer Centre. He is also the Co-Director of the Pancreatic
Cancer Research Initiative at the Ontario Institute of Cancer Research and a Scientist in the
Division of Experimental Therapeutics at the Ontario Cancer Institute.
Dr. Moore’s major research interest over the past 10 years has been innovative drug
development for cancer therapy, and he has been a Principal Investigator for many Phase I, II
and III studies in gastrointestinal and genitourinary cancer. Dr. Moore has published over 200
peer-reviewed manuscripts, review articles, and book chapters and is on the editorial board of
the Journal of Clinical Oncology. He has presented nationally and internationally, having given
over 150 invited lectures worldwide.
Dr. Christopher J. Paige, PhD, FCAHS
Vice President, Research, University Health Network, Toronto General
Hospital, Toronto Western Hospital, Princess Margaret Cancer Centre,
Toronto Rehabilitation Institute
Ronald Buick Chair in Cancer Research, Ontario Cancer Institute
Since 1998, Dr. Paige has been Vice President, Research of the Ontario Cancer Institute and
has since assumed his current position of Vice President, Research at the University Health
Network, which comprises four hospitals: Toronto Rehab, Toronto General Hospital, Toronto
Western Hospital and Princess Margaret Cancer Centre.
Dr. Paige is an internationally recognized leader in the area of lymphocyte development and
antibody formation, with an active research program in training the immune system to recognize
cancer cells. He is the recipient of the Cinader Award of the Canadian Society of Immunology,
Salute to the City Award of the City of Toronto, and the UFCW Canada Research Award of the
Leukemia Society of Canada. He is a Fellow of the Canadian Academy of Health Sciences.
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Dr. Li Zhang, MD, PhD
Research Director, University of Toronto Transplantation Institute
Inaugural Maria H. Bacardi Chair in Transplantation
Senior Scientist, Toronto General Research Institute, University Health
Network
Dr. Zhang currently holds a Maria H. Bacardi Chair in Transplantation and is also the Research
Director of the University of Toronto Transplantation Institute. Her research has been focused
on understanding the cellular and molecular mechanisms involved in immune tolerance and its
applications in various diseases including graft rejection, graft versus host disease, autoimmune
diseases and cancer.
Dr. Zhang’s laboratory was the first to discover and characterize a subset of T lymphocytes
termed double negative (DN) T-cells. Her group and other laboratories have demonstrated that
DN T-cells can prevent transplant rejection, inhibit graft versus host disease and autoimmune
disease, and eliminate cancer cells. Dr. Zhang’s group is currently dissecting further the
molecular mechanisms involved in DN T-cell action and building a critical bridge between new
concepts originating from her laboratory and novel immunotherapy for cancer patients.
The Princess Margaret Cancer Foundation | Page 22
To donate or find out more information
about the Immune Therapy Program,
please contact:
Shannon Stuart
Director, Major Gifts
(416) 946-6571
[email protected]
The Princess Margaret Cancer Foundation | Page 23