Cellectis Publishes Article in Frontiers in Immunology Unveiling Pre-Clinical Data on a Novel Treatment Paradigm for Successful CAR T Immunotherapy Against Stroma-rich Solid Tumors
12 Mai 2023 - 7:30AM
Cellectis Publishes Article in Frontiers in Immunology Unveiling
Pre-Clinical Data on a Novel Treatment Paradigm for Successful
CAR T Immunotherapy Against Stroma-rich Solid Tumors
Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS),
a clinical-stage biotechnology company using its pioneering
gene-editing platform to develop life-saving cell and gene
therapies, today published an article in Frontiers Bioenginnering,
demonstrating the efficacy of its TALEN® engineered FAP UCART-cells
in cancer-associated fibroblast (CAF) depletion, reduction of
desmoplasia and tumor infiltration.
Adoptive cell therapy based on chimeric antigen
receptor-engineered T (CAR-T) cells has proven to be lifesaving for
many cancer patients.
However, its therapeutic efficacy has so far
been restricted to only a few malignancies, with solid tumors
proving to be especially recalcitrant to efficient therapy. Poor
intra-tumor infiltration by T cells and T cell dysfunction due to a
desmoplastic, immunosuppressive microenvironment are key barriers
for CAR T-cell success against solid tumors.
Cancer-associated fibroblasts (CAFs) are
critical components of the tumor stroma, evolving specifically
within the tumor microenvironment (TME). The CAF secretome is a
significant contributor to the extracellular matrix and a plethora
of cytokines and growth factors that induce immune suppression.
Together they form a physical and chemical barrier which induces a
T cell-excluding ‘cold’ TME. CAF depletion in stroma rich solid
tumors can thus provide an opportunity to convert immune evasive
tumors susceptible to tumor-antigen CAR T-cell cytotoxicity.
Cellectis used its TALEN®-based gene editing
platform to engineer non-alloreactive, immune-evasive UCAR T-cells
targeting the unique CAF marker Fibroblast Activation Protein,
alpha (FAP) to test whether FAP UCAR T-cell pre-treatment can make
‘cold’ tumors susceptible to subsequent tumor-antigen targeting CAR
T-cells. Cellectis also generated non-alloreactive CAR T-cells
against the tumor associated antigen (TAA) Mesothelin which is
overexpressed in most solid tumors including mesothelioma and large
sub-sets of ovarian, breast, pancreatic and lung adenocarcinomas.
The combination treatment strategy was tested in a pre-clinical
mouse model of triple-negative breast cancer (TNBC), an aggressive,
stroma-rich breast cancer sub-type with poor prognosis and very
limited treatment options at present.
“Over 90% of epithelial cancers including
breast, colorectal, pancreatic and lung adenocarcinomas express the
CAF-specific surface marker, fibroblast activation protein α (FAP),
which makes it a promising CAR T-cell target. In this study, we
propose a novel and versatile approach of combination CAR T-cell
therapy that can be extended to most stroma-rich cold tumors with
relevant tumor-antigen targeting CAR T-cells which otherwise are
recalcitrant to cell therapy”, said Shipra Das, Ph.D., Senior
Scientist & Team Leader at Cellectis.
Preclinical data showed
that:
- In a mouse xenograft model,
successful implantation of injected CAFs in the tumors was
confirmed by positive staining of spindle-like cells with
human-specific FAP antibody, recapitulating a physiologically
relevant TNBC tumor with tumor and stromal compartments.
- FAP UCART-cells alone significantly
reduced tumor growth.
- In vitro and in vivo results show
that FAP UCART-cells enable the reprogramming of the cold,
stroma-rich triple negative breast cancer (TNBC) TME, making the
tumor susceptible to subsequent Meso UCAR T infiltration and
cytotoxicity and improving the overall antitumor activity of the
treatment.
- In the context of combination
therapy with anti-PD1 checkpoint inhibitor, maximal anti-tumor
activity and survival benefits were observed upon FAP UCAR T-cell
treatment followed by Meso UCAR T-cell treatment.
This article is available on Frontiers
Bioengineering website by clicking on this link.
About Cellectis
Cellectis is a clinical-stage biotechnology
company using its pioneering gene-editing platform to develop
life-saving cell and gene therapies. Cellectis utilizes an
allogeneic approach for CAR-T immunotherapies in oncology,
pioneering the concept of off-the-shelf and ready-to-use
gene-edited CAR T-cells to treat cancer patients, and a platform to
make therapeutic gene editing in hemopoietic stem cells for various
diseases. As a clinical-stage biopharmaceutical company with over
23 years of experience and expertise in gene editing, Cellectis is
developing life-changing product candidates utilizing TALEN®, its
gene editing technology, and PulseAgile, its pioneering
electroporation system to harness the power of the immune system in
order to treat diseases with unmet medical needs. Cellectis’
headquarters are in Paris, France, with locations in New York, New
York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq
Global Market (ticker: CLLS) and on Euronext Growth (ticker:
ALCLS). For more information, visit www.cellectis.com. Follow
Cellectis on social media: @cellectis, LinkedIn and YouTube.
Forward-looking Statements
This press release contains “forward-looking”
statements within the meaning of applicable securities laws,
including the Private Securities Litigation Reform Act of 1995.
Forward-looking statements may be identified by words such as
“anticipate,” “believe,” “intend”, “expect,” “plan,” “scheduled,”
“could,” “would” and “will,” or the negative of these and similar
expressions. These forward-looking statements, which are based on
our management’s current expectations and assumptions.
Forward-looking statements include statements about the potential
of the innovations of the Company. These forward-looking statements
are made in light of information currently available to us and are
subject to numerous risks and uncertainties, including with respect
to the numerous risks associated with biopharmaceutical product
candidate development. With respect to our cash runway, our
operating plans, including product development plans, may change as
a result of various factors, including factors currently unknown to
us. Furthermore, many other important factors, including those
described in our Annual Report on Form 20-F and the financial
report (including the management report) for the year ended
December 31, 2022 and subsequent filings Cellectis makes with the
Securities Exchange Commission from time to time, as well as other
known and unknown risks and uncertainties may adversely affect such
forward-looking statements and cause our actual results,
performance or achievements to be materially different from those
expressed or implied by the forward-looking statements. Except as
required by law, we assume no obligation to update these
forward-looking statements publicly, or to update the reasons why
actual results could differ materially from those anticipated in
the forward-looking statements, even if new information becomes
available in the future.
For further information, please
contact:
Media contact:
Pascalyne Wilson, Director, Communications, +33
(0)7 76 99 14 33, media@cellectis.com
Investor Relation contacts:
Arthur Stril, Chief Business Officer, +1 (347)
809 5980, investors@cellectis.comAshley R. Robinson, LifeSci
Advisors, +1 617 430 7577
- FAP scientific article PR
Cellectis Nom Eo 05 (EU:ALCLS)
Graphique Historique de l'Action
De Avr 2024 à Mai 2024
Cellectis Nom Eo 05 (EU:ALCLS)
Graphique Historique de l'Action
De Mai 2023 à Mai 2024