Allogene Therapeutics Presents Preclinical Data on Next Generation Cloak™ and Dagger™ Technologies at the Society for Immunotherapy of Cancer Annual Meeting
03 Novembro 2023 - 1:00PM
Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage
biotechnology company pioneering the development of allogeneic CAR
T (AlloCAR T™) products for cancer, today presented data
highlighting the Company’s next generation Cloak™ and Dagger™
technologies designed to help enhance engraftment, expansion and
the persistence of AlloCAR T cell candidates, at the Society for
Immunotherapy of Cancer (SITC) Annual Meeting November 1-5, 2023,
in San Diego, CA.
The development of “off-the-shelf” CAR T products that utilize
cells from healthy donors has the potential to make CAR T therapies
scalable and accessible to more patients. However, the
effectiveness of allogeneic CAR T cells requires controlling
rejection of the allogeneic CAR T cells by the patient’s immune
system. Allogene’s proprietary Cloak and Dagger technologies are
two novel strategies the Company is investigating to help control
immune rejection and enhance expansion, persistence, and
performance of AlloCAR T cells with the use of standard
lymphodepletion regimens.
“These promising data show that both our Cloak and Dagger
technology platforms can engineer AlloCAR T cells to minimize the
potential of rejection by host immune cells, without impacting
performance and in some cases, enhancing efficacy,” said Zachary
Roberts, M.D., Ph.D., Executive Vice President, Research &
Development and Chief Medical Officer of Allogene. “These
innovative approaches are intended to simplify the lymphodepletion
requirement for allogeneic CAR T products, and may provide a path
to further expand the potential of off-the-shelf CAR T products
beyond current targets and indications.”
The Cloak platform technology is designed to prevent AlloCAR T
cells from being recognized by host T cells without triggering
substantial natural killer (NK) cell rejection while preserving CAR
T cell function. Data shown previously demonstrated that knockout
of RFX5, a transcriptional regulator that controls expression of
HLA molecules, enhanced survival of allogeneic CAR T cells in the
presence of host T cells and elicited only minor NK cell
reactivity, thereby effectively mitigating rejection.
This preclinical study evaluated an additional anti-rejection
approach to immune evasion by inactivating CD58 and ICAM-1, key
components of the immune synapse required for effective recognition
and lysis by alloreactive T/NK cells. In the study, the survival of
“cloaked” cells was assessed in mixed lymphocyte reaction assays
with T cells and NK cells. The knockout of CD58 and ICAM-1
effectively reduced T cell rejection of allogeneic CAR T cells
without triggering NK cell rejection or impacting effector function
and worked additively with the knockout of RFX5.
The Dagger platform technology arms AlloCAR T cells with a CD70
CAR designed to recognize and deplete CD70-positive host immune
cells while enabling tumor-targeting anti-CD19 AlloCAR T cells to
resist rejection from the host immune cells. This endows the
CAR-expressing T cells with dual specificity against tumors that
co-express CD19 and CD70, which includes approximately 70% of
patients with large B-cell lymphoma (LBCL). As a result, this
potential advance provides both a prolonged window of persistence
during which AlloCAR T cells can expand and actively target and
destroy cancer cells as well as insure against CD19 loss-mediated
tumor escape, a known mechanism of resistance to CD19 CAR T
therapy.
The Dagger technology, a feature of our ALLO-316 candidate, has
clinically demonstrated its unique immunomodulatory effect,
contributing to robust AlloCAR T cell expansion and persistence
even with relatively lower doses of CAR T cells and lymphodepletion
than in other AlloCAR T programs. The ongoing Phase 1 dose
escalation TRAVERSE study using investigational ALLO-316 in
patients with advanced or metastatic renal cell carcinoma (RCC) who
have progressed on standard therapies including an immune
checkpoint inhibitor and a VEGF-targeting therapy.
About Allogene TherapeuticsAllogene
Therapeutics, with headquarters in South San Francisco, is a
clinical-stage biotechnology company pioneering the development of
allogeneic chimeric antigen receptor T cell (AlloCAR T™) products
for cancer. Led by a management team with significant experience in
cell therapy, Allogene is developing a pipeline of “off-the-shelf”
CAR T product candidates with the goal of delivering readily
available cell therapy on-demand, more reliably, and at greater
scale to more patients. For more information, please visit
www.allogene.com, and follow @AllogeneTx on X (formerly Twitter)
and LinkedIn.
Cautionary Note on Forward-Looking Statements for
AllogeneThis press release contains forward-looking
statements for purposes of the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. The press release
may, in some cases, use terms such as “advance,” "predicts,"
"believes," "potential," "proposed," "continue," "estimates,"
"anticipates," "expects," "plans," "intends," "may," "could,"
"might," "will," "should" or other words that convey uncertainty of
future events or outcomes to identify these forward-looking
statements. Forward-looking statements include statements regarding
intentions, beliefs, projections, outlook, analyses or current
expectations concerning, among other things Allogene’s ability to
develop and deliver readily available allogeneic CAR T products for
cancer treatment on-demand, more reliably, and at greater scale to
more patients. Various factors may cause material differences
between Allogene’s expectations and actual results, including risks
and uncertainties related to: our product candidates are based on
novel technologies, which makes it difficult to predict the time
and cost of product candidate development and the likelihood of
obtaining regulatory approval; the extent to which
the FDA disagrees with our clinical or regulatory plans,
which could cause future delays to our clinical trials or require
additional clinical trials; and we may not be able to demonstrate
the safety and efficacy of our product candidates in our clinical
trials, which could prevent or delay regulatory approval and
commercialization. These and other risks are discussed in greater
detail in Allogene’s filings with the SEC, including without
limitation under the “Risk Factor” Heading in its Form 10-Q filed
for the quarter ended September 30, 2023. Any forward-looking
statements that are made in this press release speak only as of the
date of this press release. Allogene assumes no obligation to
update the forward-looking statements whether as a result of new
information, future events or otherwise, after the date of this
press release.
AlloCAR T™, Cloak™ and Dagger™ are trademarks of Allogene
Therapeutics, Inc.
Allogene’s AlloCAR T™ programs utilize Cellectis technologies.
The anti-CD70 AlloCAR T programs are licensed exclusively from
Cellectis by Allogene and Allogene holds global development and
commercial rights to these AlloCAR T programs.
Allogene Media/Investor Contact:Christine
CassianoChief Corporate Affairs & Brand Strategy
OfficerChristine.Cassiano@allogene.com
Additional Allogene Media Contacts:Leslie
BryantLeslie.Bryant@allogene.com
Madeleine GoldsteinMadeleine.Goldstein@allogene.com
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