Cellectis Publishes Novel Methods to Improve the Safety of CAR T-Cell Therapy and Prevent CRS in the Journal of Biological Chemistry
Business Wire 25-Feb-2019 5:10 PM
Granulocyte-macrophage colony-stimulating factor inactivation in
CAR T-Cells prevents monocyte-dependent release of key cytokine release
syndrome mediators
Regulatory News:
Cellectis
(Paris:ALCLS) (NASDAQ:CLLS) ((Euronext Growth: ALCLS, NASDAQ:CLLS), a
biopharmaceutical company focused on developing immunotherapies based on
allogeneic gene edited CAR T-cells (UCART), today announced the
publication of a study in The Journal of Biological Chemistry,
identifying Granulocyte Macrophage Colony Stimulating Factor (GMCSF)
secreted by Chimeric Antigen Receptor (CAR) T-cells as a key factor
promoting cytokine release syndrome (CRS). The accelerated report
leverages these findings to elaborate an innovative engineering strategy
that paves the way for developing safer UCART products.
Utilizing these results, Cellectis developed engineered GMCSF Knock-Out
CAR T-cells through TALEN®-mediated gene inactivation. The
inactivation of GMCSF in CAR T-cells was found to prevent secretion of
pro-inflammatory cytokines by monocytes, without compromising CAR T-cell
anti-tumor activity.
"CAR T-cells have achieved high rates of complete remission in
hematological malignancies, however, this 'living drug' can show
life-threatening inflammatory side effects including CRS and
neurotoxicity that need to be addressed," said Mohit Sachdeva, Ph.D.,
Innovation Project Leader at Cellectis. "Our engineering strategy
circumvents such toxic side effects and propose safer, equally potent
UCART-cells, to improve patients' quality of life during treatment."
"Today, tocilizumab or glucocorticoid treatments are considered the
standard of care for CRS management," added Julien Valton, Ph.D.,
Innovation Team Leader at Cellectis. "However, these treatments increase
patient medication burden, add substantial costs and lengthen treatment
time in intense care settings. To overcome these clinical challenges, we
investigated the biogenesis of CRS and based on our findings, developed
a CAR T-cell product candidate that could potentially prevent rather
than treat CRS symptoms. We hope this approach can bypass CRS
symptomatic treatments and improve the overall safety of CAR T-cell
therapies for cancer patients."
Julien Valton, Ph.D., Innovation Team Leader, Cellular Engineering &
Adoptive CAR T-Cell Immunotherapy
Dr. Julien Valton obtained his Ph.D. at the University Joseph Fourier in
Grenoble, France, where he was trained as an enzymologist. He then
joined the Yale School of Medicine to apply his knowledge to therapeutic
research by investigating the mechanism of inhibition of receptor
tyrosine kinases that are involved in the development of
gastrointestinal cancer. In 2009, he moved a step further into the field
of applied science by joining the Innovation Department of Cellectis,
where he actively participated in using and improving TALEN®
gene editing technology for targeted gene therapy and genome
engineering. He is now using TALEN® along with protein
engineering techniques to develop the next-generation CAR T-cells to
treat different malignancies.
Mohit Sachdeva, Ph.D., Innovation Team Senior Scientist
Dr. Sachdeva is an experienced cancer biologist with expertise in
immuno-oncology, having authored/co-authored approximately 20
manuscripts in peer-reviewed journals throughout his career. During his
time at Cellectis, he has been studying pathways that could be exploited
to engineer potent, yet safer, CAR T-cells using gene editing and
targeted integration technologies. After receiving his Ph.D. at Southern
Illinois University, he completed a successful post-doc at Duke
University.
Granulocyte-macrophage
colony-stimulating factor inactivation in CAR T-Cells prevents
monocyte-dependent release of key cytokine release syndrome mediators
Mohit Sachdeva1*, Philippe Duchateau2,
Stéphane Depil2, Laurent Poirot2
and Julien Valton1*
1Cellectis, Inc., 430 East 29th Street, New York,
NY 10016, USA2Cellectis, 8 rue de la
Croix Jarry, 75013 Paris, France
About Cellectis
Cellectis is a clinical-stage biopharmaceutical company focused on
developing a new generation of cancer immunotherapies based on
gene-edited T-cells (UCART). By capitalizing on its 19 years of
expertise in gene editing – built on its flagship TALEN®
technology and pioneering electroporation system PulseAgile – Cellectis
uses the power of the immune system to target and eradicate cancer cells.
Using its life-science-focused, pioneering genome engineering
technologies, Cellectis' goal is to create innovative products in
multiple fields and with various target markets. Cellectis is listed on
the Nasdaq (NASDAQ:CLLS) and on Euronext Growth (TICKER:ALCLS). To
find out more about us, visit our website: www.cellectis.com
Talking about gene editing? We do it. TALEN® is a registered
trademark owned by Cellectis.
Disclaimer
This press release contains "forward-looking" statements that are based
on our management's current expectations and assumptions and on
information currently available to management. Forward-looking
statements involve known and unknown risks, uncertainties and other
factors that may cause our actual results, performance or achievements
to be materially different from any future results, performance or
achievements expressed or implied by the forward-looking statements.
Further information on the risk factors that may affect company business
and financial performance is included in Cellectis' Annual Report on
Form 20-F and the financial report (including the management report) for
the year ended December 31, 2017 and subsequent filings Cellectis makes
with the Securities Exchange Commission from time to time. 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.
View source version on businesswire.com: https://www.businesswire.com/news/home/20190225006073/en/
