BC Cancer - Winter 2017 - 7

RESEARCHER PROFILE

Meet Dr. Robert Holt
Sequencing and engineering DNA to ﬁnd cancer cures
Dr. Robert Holt is a distinguished scientist at BC Cancer's Genome Sciences Centre (GSC) and co-director of BC Cancer's
immunotherapy program. Born and raised in Vancouver, Dr. Holt spent his early career in the United States, and
played a key role in the initial sequencing of the human genome. Now he and his team have moved from reading DNA
code to writing it. His lab is working on a promising new type of gene therapy that combines state-of-the-art genetic
engineering with immunology. He believes the work will lead to therapies that ensure the immune system wins.

DISCOVERY: What drew you to
the study of DNA and cancer?
DR. HOLT: I was drawn into the enormous effort to decode the human
genome because, in addition to offering the first view of the code of life, it
was key to understanding how mutations that alter the genome can result
in cancer. These efforts are ongoing
today at the GSC, where we sequence
thousands of cancer genomes per year.
It is clear now that no two cancers are
exactly alike; it's the most challenging
genetic disease.

DISCOVERY: From your perspective,
what's the most promising area of
cancer research today?
DR. HOLT: Unfortunately there is no
way to fix mutations to reverse cancer,
just like there is no way to unscramble
an egg. Cancer cells simply need to be
eliminated, and the best way to do this
is to rely on your own immune system.
Although the immune system has the
potential ability to recognize mutated
cancer cells as foreign and kill them,
it has trouble distinguishing cancer
cells from healthy cells and allows
the cancer cells to grow. Now, with
our relatively new ability to analyze
and manipulate DNA, we can actually hardwire a patient's own immune

cells through genetic engineering to be
extremely effective in recognizing and
eliminating some types of cancer cells,
mainly leukemia and lymphoma cells.
With further research, it's hoped that
this type of therapy can be applied to a
broader range of cancers.

DISCOVERY: What is CAR-T cell
therapy and your lab's role in
developing this treatment?
DR. HOLT: Well, let's unpack the name.
A T cell is a type of natural immune
cell that ordinarily recognizes and
kills virus-infected cells. CAR stands
for chimeric antigen receptor. An
"antigen" is a feature on a cancer cell
that can be recognized by a "receptor"
on the T cell. In CAR-T cell therapy a
gene that encodes a new, synthetic
receptor is directly introduced into a
patient's own T cells. This allows the
T cell to wake up, recognize the antigen and, when re-infused back into
the patient, selectively eliminate the
cancer cells.
Importantly, there are currently no
CAR-T cell therapy options in Canada.
At BC Cancer, we are leading a new
national program to manufacture
CAR-T cells and confirm their safety
and efficacy. This is necessary to gain
Health Canada approval and make the

therapy available to Canadian patients
in need as quickly as possible.

DISCOVERY: How does support
from BC Cancer Foundation
donors impact your work?
DR. HOLT: Support from BC Cancer
Foundation donors is critical to all
aspects of this work. Donations underpinned much of the early stage research
that allowed us to scale up this program.
Further, some resources are currently
only available to us through donor support. For example, many aspects of
manufacturing and clinical testing can't
be supported through conventional
research grants because they fall outside
of the usual definition of basic research.
In situations where we are eligible for
research grants they are typically only
given as matching funds, so in many
situations recently we have been
able to leverage the amount provided
through donors and obtain twice the
funds. In fact, this is how we launched
our CAR-T program.
I would like to give special thanks
to the Conconi family, who provided
the initial investment to build the
Conconi Family Immunotherapy Lab,
which has been absolutely central to
the development of CAR-T cell therapy
in our province.

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Table of Contents for the Digital Edition of BC Cancer - Winter 2017