CANCER • CONTINUED FROM THE PREVIOUS PAGE
Drs. Verneris and Fry will also be a part of
bringing those new treatments, including CD19,
from academic supercenters like Children’s
Colorado to the patients who need them,
wherever they are. Working within a consortium
funded by the National Institutes of Health and
the Clinical & Translational Science Institute,
they’re working to help smaller centers get CAR
therapies online. Biomanufacturing Facility brought CAR cell
manufacturing online last year.
“Right now it’s largely hub and spoke,” says
Dr. Verneris. “This work will help set up smaller
pediatric hospitals that just don’t have the staff
at the moment to deal with the massive amount
of regulation.” This year, they’ll make CD19 for a trial that
seeks to expand access to commercial therapy.
As it stands, patients must have competed
their first chemotherapy regimen, relapsed,
and undergone and failed yet another round of
“salvage” chemotherapy before they’re eligible.
Dr. Fry wants to see CD19 move up to the first
relapse — maybe even, eventually, up front.
That’s a tough hurdle to clear for any
institution. Across the Anschutz Medical
Campus from Children’s Colorado, the Gates
“Our job is to set up a platform to allow efficient
transfer from research to clinic,” says Ryan
Crisman, PhD, Gates’s Director. In collaboration
with Dr. Fry, Gates is positioned to manufacture
cells for a wide array of future trials — some in
the planning stages, many not yet conceived.
It’ll take smart, driven, creative people working
together across institutions to realize that goal.
But perhaps most of all, says Dr. Fry, it will take
the happy accidents those relationships afford.
“We come up with our ideas in the lab, but
the best ones come from conversations in the
hallway with someone not at all involved, who
thinks completely differently than we do and
asks a question we’ve never thought of asking,”
he says. “And that leads to a collaboration, which
leads to the next breakthrough. That’s always
how it goes.” ●
To see more about cellular therapy
at Children’s Colorado, visit
childrenscolorado.org/CAR-T.
As a facility that collects, processes, stores
and matches stem cells used in bone marrow
transplant for institutions all over the world,
ClinImmune has infused cell products into
thousands of patients. As its Executive Director,
Dr. Freed is well familiar with the kind of
paperwork that requires.
“This is one of three volumes,” he remarks.
Infusing cell products into humans, on a procedural
level, is incredibly complex. It requires a rigorous
precision of equipment and expertise. That’s
particularly true for the manufacture of CARs.
“It’s a patient-specific drug, there’s HIV-based
vectors and it involves genetic engineering,” says
8
U.S. News & World Report Pediatric Cancer
Center since inception of the ranking
400+
Ongoing clinical trials across all disciplines
1,000+
GMP for dummies
Brian M. Freed, PhD, drops a heavy binder on his
desk. Its contents: about 800 pages of standard
operating procedures for cell handling at
ClinImmune, a transplant immunology lab right
next door to the Gates Center on the Anschutz
Medical Campus.
TOP 10
Dr. Fry. “These are the components that make
people nervous.”
Conceived as a stem cell research lab, the Gates
Center had good bones for Good Manufacturing
Practice, or GMP, as it’s known. They had the right
equipment and facilities, and they had many of the
right people. What they lacked was the regulatory
infrastructure, which involves paperwork — and
people with the training to do it — on a mind-
boggling scale. For that, they collaborated with
ClinImmune, a lab intimate with cell-infusion’s
many regulatory demands.
“Batch records run 500 pages. There’s a 400-page
document just about training staff,” says Dr. Fry.
“It’s thousands and thousands of pages.
“To be clear,” he adds, “that’s a good thing.”
“If we infuse one of these products into a patient
and 30 days later there’s some adverse event,
we want to know why,” notes Tim Gardner, Gates
Center’s Chief Financial Officer. “Then we can
look at the documentation and know everything
there is to know about how it was manufactured:
the humidity level in the room, the particle count,
the people, the practices, the equipment, when it
was last maintained and how. We have one person
documenting for every person doing.”
With five cell therapy suites, each of which can run
different products, the Gates Center has capacity
to do a lot. They’ll produce cells for innumerable
novel CAR therapies. Some of them — CARs
targeting CD19 and CD22, another for CD33 and
another for TSLPR — will come online in trials just
this year.
“We took all the time we needed to get this facility
to the point where they could support multiple
human trials,” says Dr. Fry. “We want to do it right.
We’re not satisfied with just getting by.”
“If we’re going to do it,” Dr. Freed notes, “we’re
going to need all hands on deck.”
Bone marrow transplants performed in
25-year program history
1
OF
ONLY
2
Pediatric health care systems in the western
region offering CAR-T cell therapy
LARGEST
Treatment center for bleeding and clotting
disorders in the western region
LEADERSHIP:
Lia Gore, MD
Chief, Pediatric Oncology, Hematology
and Bone Marrow Transplant,
The Ergen Family Chair in Pediatric Cancer
For cancer healthcare professional resources,
visit childrenscolorado.org/CancerHCP.
NEW CONSTELLATIONS
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