SOUTH SAN FRANCISCO, Calif.,
July 21, 2019 /PRNewswire/
-- PACT Pharma, a leader in the fields of cancer immunology
and cell therapy in collaboration with a team at UCLA, presented new data demonstrating for the
first time the ability to identify mutation targets unique to each
person's cancer and verify the cancer specificity of multiple
cloned T cell receptors. Each patient's cancer has a private
signature of mutations, creating an opportunity to develop fully
personalized immune therapies that have the potential to eradicate
tumor cells. Defining these cancer mutation targets for each
person, known as neoantigens, enables the company to use its
proprietary gene engineering technologies to manufacture an immune
cell therapy product for each person with cancer. The presentation
was at the AACR's Special Conference on Immune Cell Therapies for
Cancer. The company has begun enrolling patients with advanced
solid tumors in its Phase 1 dose escalation study of NeoTCR-P1, an
autologous gene-edited TCR T cell product that targets personalized
neoantigens (https://clinicaltrials.gov/ct2/show/NCT03970382).
"These exciting results open a bold new frontier for directing a
person's own immune system to treat patients with solid cancers, an
area that hasn't yet seen the successes of immune cell therapies
that we have seen for blood cancers," said PACT's Chief Executive
Officer Alex Franzusoff, Ph.D.
"While it is early, the results demonstrate the possibility for
PACT's approach to ignite a patient's immune response directly
against their unique tumor mutation signature, within a clinically
relevant timeframe, with potential applicability to most cancers
and all ethnicities across the globe."
Today's data is relevant because they show that mutations that
build up in tumors, creating the unique tumor mutation "signature"
that drives each patient's cancer, have already triggered each
person's immune system to target those unique mutations, but at a
very low level. Now those low-level targeted immune responses can
be analyzed with greater accuracy, used to manufacture a truly
personalized treatment that is tailored for each patient with
cancer, and evaluated in clinical trials.
The company's approach is designed to select and confirm
tumor-exclusive mutations to empower a patient's immune system to
target their specific cancer. PACT utilizes bioinformatics to
identify the mutation blueprint of each person's tumor, and then
uses its barcoded snare technologies to capture pre-existing T
cells from the blood that already recognize and target the unique
mutations. From that group, a proprietary selection platform is
used to identify the ideal T cell receptors for specific mutations.
Once the target is authenticated, the company uses non-viral gene
editing to engineer the ideal mutation-targeted T cell receptors
into T cells from the same patient. When reinfused back to the
patient, these T cells have the potential to eliminate tumor cells
that express these unique mutations.
"The results presented today show that PACT's approach of
neoantigen-specific T cell capture and non-viral precision genome
engineering is indeed groundbreaking and promising for a new
chapter in personalized immune cell therapies for patients with
solid cancers," said Antoni Ribas, a
professor of medicine at the Jonsson Comprehensive Cancer Center at
the University of California, Los
Angeles, who is a co-author of the study and also a
co-founder of PACT. "The demonstration that T cell
receptor-engineered T cells using the PACT approach can
specifically kill that same person's cancer cells is based on the
analysis of immune cells captured from the blood of a patient with
a long-lasting response to anti-PD-1 therapy."
The evolution of personalized immune-oncology treatments
Recently, a new generation of personalized cellular therapies for
cancer has emerged. Rapid sequencing technologies, bioinformatics,
and genetic/cellular engineering — in addition to a deeper
understanding of clinical immunology and a renaissance in
immunotherapy — have made these advancements possible. Designer
immune-oncology treatments have been developed, including CAR-T
cell therapies, cancer vaccines and tumor-infiltrating lymphocyte
therapies.
While transformative, these therapeutic approaches face
limitations. CAR-T cells only recognize shared cancer targets
expressed on the cell surface, which, while effective for blood
cancers, have not been applied successfully to patients with solid
cancers, and cancer vaccines are often too slow to address a
rapidly growing tumor burden. Further, tumor-infiltrating
lymphocytes can be impractical—and at times even impossible—to
generate for every patient due to the difficulty of isolating
limited numbers of specific tumor-targeting immune cells and then
needing to greatly expand their numbers for patient dosing. In the
case of expanded immune cells in particular, they often become
exhausted before reinfusion, which may limit their value for
eliminating the cancer throughout the body.
In order to truly tailor cancer treatments to individuals, the
therapy must target each patient's unique cancer
signature--including different tissue compatibility receptors of
the immune system, or HLA, in each person. These HLA receptors are
key to immune recognition, which is what limits organ sharing
between people. PACT's approach captures this nuance. Custom
tailored, yet for a global population, PACT's approach is designed
to select and authenticate tumor-exclusive mutations to empower the
patient's immune system to target their specific cancer for a
lasting effect. PACT plans to further investigate the safety and
effectiveness of this technology in a series of clinical trials,
starting with a first-in-human Phase 1 clinical trial at clinical
sites in California.
ABOUT PACT –
PACT Pharma is an independent,
privately funded company, based in South
San Francisco, California, developing transformational
personalized TCR-T cell therapies for the eradication of solid
tumors and is now enrolling patients in its first-in-human Phase 1
clinical studies at several key academic centers of the CIRM-funded
Alpha Clinic network, in California.
PACT Pharma's accomplished co-founders, David Baltimore (Nobel Laureate), Antoni Ribas, Jim
Heath, Terry Rosen and
Juan Jaen, established the company
in 2016 and launched the company in early 2017. The PACT team
raised $31 million in 2016 and
secured another $95 million in
financing in May of 2018 from Alphabet Inc.'s venture arm GV
Investments, Canaan Partners, Casdin Capital, Droia, Foresite
Capital, Invus, Pontifax and Wu Capital, including investment from
AbbVie Ventures and Taiho Ventures.
PACT Pharma's technology is designed to reprogram a patient's
immune system cells to target their own cancer. The process
involves taking a biopsy of a person's cancer tissue, sequencing
the tumor's DNA and then using predictive algorithms and
proprietary technologies to engineer T-cells involved in the
body's immune response to combat that specific disease as it
expresses itself in the patient. The last step is injecting the
cocktail back into the patient.
Tumor mutation targeting is programmed into the patient's own T
cells to seek out and kill the tumors. Using (non-viral)
precision genome engineering, the mutation-targeted T cell
receptors (neoTCRs) are designed to replace the pre-existing T cell
receptors of fresh CD8 and CD4 T-cells collected from that same
patient followed by minimal expansion in closed systems for
re-infusion into the patient. These patient-specific neoTCR-P1
cells are formulated to immediately kill neoantigen-expressing
tumors, together with a deep reservoir of 'ready-to-go'
neoTCR-P1 cells for long term persistence and which may be capable
of rapid expansion to prevent future cancer recurrence.
CONTACT: William Nevius,
wnevius(at)canaan.com
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SOURCE PACT Pharma