ASH Clinical News ACN_4.13_full issue_Web | Page 23

UP FRONT
and our children, and I am so grateful for
their support.
In my medical career, my greatest ac-
complishment has been my involvement
in the field of tumor immunotherapy. I
have been fortunate to participate in the
development of new therapeutics that
use the body’s immune system to treat
cancer, including demonstrating for the
first time that transplanted donor T cells
could eradicate widely metastatic and
treatment-refractory kidney cancer.
This involved going back to
formulas in the laboratory to un-
derstand the mechanisms of disease
resistance, dissecting the exact
target of these immune effects, and
identifying the target antigen. In the
lab, we found a human endogenous
retrovirus that was expressed in most
cancerous kidney tumors; using that
virus as our target, we identified the
exact molecular mechanisms that led
to its selective expression in kidney
cancer.
More recently, we have cloned T-
cell receptors that recognize peptides
and proteins derived from this virus.
We have demonstrated the ability to
transduce human T cells to express
T-cell receptors that target the virus.
We have taken this approach from
bench to bedside and are now about
to treat patients with metastatic kid-
ney cancer using their own modified
T cells.
“There’s only
one thing
that I feel like
I could ever
have done,
and that is to
be a physician.
It’s been
my lifelong
passion.”
I started conducting the research, I knew
that this idea was off-the-wall; luckily, the
NIH is supportive of cutting-edge, first-
in-human, paradigm-shifting research.
What disappointments have you
experienced in your career, and
how have you handled them?
The biggest disappointments relate to
the ever-increasing number of regula-
tory requirements and hurdles that stand
between investigators and cutting-edge
clinical research. While I realize that
these processes are necessary and impor-
tant to ensuring patient safety and the in-
tegrity of the science that we perform, it
is becoming progressively more difficult
to quickly translate our bench findings to
the clinic. This increasing oversight can
delay trial openings and make trials even
more expensive to conduct.
And despite the successes of our
kidney cancer trial, that experience was
marked with disappointments. For exam-
ple, some patients would benefit tremen-
dously from the procedure – experiencing
disease remission and cure – but many
patients did not respond to treatment.
However, those disappointments were a
major driver to try to dissect what exactly
was happening in the patients in whom
treatment was successful.
CMYK
Our understanding of multiple myeloma is evolving.
Learn how new techniques are helping to fi ght relapse.
MULTIPLE MYELOMA:
KEY STATISTICS RELAPSE AND
HETEROGENEITY THE ROLE OF
THE PROTEASOME
Second most common
blood cancer, with a
global yearly incidence
of almost 114,000 cases 1,2 Although outcomes
have improved, most
patients with multiple
myeloma inevitably
relapse 3 In multiple myeloma, normal
function of the proteasome
likely contributes to
survival and proliferation
of malignant cells 4,5
BONE DISEASE
A common complication,
bone disease develops
in up to 90% of patients
over the course of the
disease 6
Discover more at MyelomaRevealed.com
This entire process – from
proof-of-principle experiments to
manipulating a patient’s own im-
mune system to target this virus –
has taken 20 years. But it has been
an incredibly rewarding 20 years.
Also, the project was only possi-
ble through the efforts of the Nation-
al Institutes of Health (NIH). When
ASHClinicalNews.org
References: 1. American Cancer Society. Cancer Facts and Figures 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual
-cancer-facts-and-fi gures/2017/cancer-facts-and-fi gures-2017.pdf. Accessed December 21, 2017. 2. International Agency for Research on Cancer. GLOBOCAN 2012:
estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed December 8, 2017.
3. Paiva B, van Dongen JJM, Orfao A. Blood. 2015;125:3059-3068. 4. Crawford LJ, Walker B, Irvine AE. J Cell Commun Signal. 2011;5:101-110. 5. Fribley A, Wang CY.
Cancer Biol Ther. 2006;5:745-748. 6. Terpos E, Moulopoulos LA, Dimopoulos MA. J Clin Oncol. 2011;29:1907-1915.
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