SQZ Biotechnologies Tolerizing Antigen Carrier (TAC) Program Induces Antigen-Specific Immune Tolerance in Preclinical Models ...
09 6월 2021 - 7:45PM
Business Wire
Engineered TACs Prevented Hyperglycemia in Type
1 Diabetes Models by Deletion of Target T Cells and Increase of
Regulatory T Cells that Exerted Potent Bystander Suppression
Data Presented at Federation of Clinical
Immunology Societies
SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking
the full potential of cell therapies for multiple therapeutic
areas, is presenting preclinical results from the company’s
Tolerizing Antigen Carrier (TAC) program demonstrating that its
engineered TACs can drive antigen-specific immune tolerance through
key mechanisms relevant to many complex autoimmune diseases. In
models of Type 1 diabetes (T1D), SQZ™ TACs were able to delete
antigen-specific T cells, without causing non-specific immune
suppression, ultimately preventing hyperglycemia. Importantly, SQZ
TACs increased antigen-specific regulatory T cells (Tregs) that
exerted potent bystander suppression, showing the ability to
suppress pathogenic T cells with different autoantigen
specificities. Together, these results suggest that SQZ TACs are a
versatile platform for inducing antigen-specific immune tolerance.
The data will be presented on Thursday at the 2021 Federation of
Clinical Immunology Sciences (FOCIS) annual meeting.
“The holy grail for effectively treating autoimmune diseases is
the ability to precisely target autoreactive T cells without
inducing broad immunosuppression,” said Howard Bernstein, M.D.,
Ph.D., chief scientific officer at SQZ Biotechnologies. “We are
very excited to see our TACs induce multiple mechanisms of
antigen-specific tolerance with long lasting effects. We believe
the ability of our TACs to increase regulatory T cells capable of
bystander suppression may enable the development of differentiated
therapies for complex autoimmune diseases.”
Critical to the development of tolerogenic therapies for many
autoimmune diseases is the ability to regulate both autoreactive
CD4 (helper) T cells and CD8 (killer) T cells, which are often
involved in the attack seen on healthy cells in autoimmune
diseases. These preclinical studies tested SQZ TACs in multiple
models of T1D.
Major Findings from Autoimmune Disease Models:
- Disease Suppression: Engineered TACs significantly
delayed onset of disease to a median of 65 days compared to 8 days
in controls of a T1D model driven by pathogenic CD4 T cells. All
doses were administered within the first 4 days of disease
induction. In another T1D model where disease was driven by
pathogenic CD8 T cells, the TACs prevented onset of T1D for all
animals. All doses were administered within the first 2 days of
disease induction.
- Reduction of Disease Driving T Cells: TACs reduced
frequency of disease driving CD4 T cells in the pancreas 5-fold and
decreased the secretion of proinflammatory cytokine interferon
gamma – a major driver of disease in this model – by 126-fold. The
engineered TACs also reduced disease driving CD8 T cells in the
pancreas by 60-fold and decreased secretion of proinflammatory
cytokine interferon gamma by 375-fold. In addition, there was a
nearly 4-fold increase in antigen-specific apoptotic CD8 T cells in
the pancreas.
- Increase in Regulatory T Cells: In the T1D model driven
by pathogenic CD4 T cells, antigen-specific Tregs in the pancreas
increased by approximately 5-fold and the suppressor cytokine IL-10
by about 6-fold.
- Bystander Suppression: In a model where both pathogenic
CD4 and CD8 T cells were present, treatment with TACs encapsulating
CD4 antigen alone increased frequency of antigen-specific Tregs by
3.5-fold, reduced the number of CD8 T cells of a different
autoantigen specificity by 10-fold, and decreased interferon gamma
secretion by 9-fold – displaying strong bystander suppression.
These robust preclinical data demonstrate that SQZ TACs can
restore T cell tolerance to self-antigens through multiple
mechanisms and highlight the broad potential of the SQZ platform to
enable antigen-specific immunotherapies for complex autoimmune
disease.
Poster Presentation Details Title: SQZ™ TAC Cell Therapy
Platform Induces Antigen-Specific Tregs and Prevents Onset of
Diabetes in Adoptive Transfer Model Abstract Number: Th128
Poster Session: Thursday, June 10, 2021 - 4:45 PM - 5:30 PM
PDT
About Type 1 Diabetes
Nearly 1.6 million Americans are living with Type 1 Diabetes
(T1D), including about 1.4 million adults and 200,000 children and
adolescents (<20 years). Five million people in the U.S. are
expected to have T1D by 2050. A separatee CDC study of T1D cases in
youth showed that 60 percent of diagnoses occur between the ages of
5 and 14. Worldwide incidence is 15 patients diagnosed per every
100,000 people. There is no cure for T1D, and it requires chronic
disease management through exogenous insulin therapy, insulin
analogs and adjunctive treatments for glycemic control. The life
expectancy for T1D patients is 10–15 years less than the healthy
population due to hypoglycemia events and long-term risks of
cardiovascular complications, neuropathy, kidney damage, and
retinopathy. There remains significant unmet need for
disease-modifying therapeutics that address the autoimmune-mediated
attack of beta cells as a driving factor of disease
pathogenesis.
About SQZ TACs
SQZ TACs are a red blood cell-derived cell therapy candidate
being developed as an antigen-specific immune tolerance platform.
The platform is designed to leverage the natural process of RBC
clearance by professional antigen presenting cells (APCs) in the
lymphoid organs, where they engulf aged RBCs and present their
components to CD4 and CD8 T cells. This physiological mechanism is
tolerogenic by default, instructing the immune system to not mount
an attack. SQZ TACs are generated by squeezing RBCs with
disease-specific antigen and are made to appear aged. SQZ TACs are
designed to be rapidly engulfed in vivo by patient’s professional
APCs and to act as a “Trojan horse” to drive high quantities of
antigen through the tolerogenic RBC clearance process, inducing
tolerization of the patient’s T cell and antibody responses against
the specific target.
About SQZ Biotechnologies
SQZ Biotechnologies is a clinical-stage biotechnology company
focused on unlocking the full potential of cell therapies to
benefit patients with cancer, autoimmune and infectious diseases.
The company’s proprietary Cell Squeeze® technology offers the
unique ability to deliver multiple biological materials into many
patient cell types to engineer what we believe can be a broad range
of potential therapeutics. Our goal is to create well-tolerated
cell therapies that can provide therapeutic benefit for patients
and improve the patient experience over existing cell therapy
approaches. With accelerated production timelines under 24 hours
and the opportunity to eliminate preconditioning and lengthy
hospital stays, our approach could change the way people think
about cell therapies. The company’s first therapeutic applications
seek to generate target-specific immune responses, both in
activation for the treatment of solid tumors and in immune
tolerance for the treatment of unwanted immune reactions and
autoimmune diseases. For more information, please visit
www.sqzbiotech.com.
Forward Looking Statement
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. All statements contained that do not relate to matters of
historical fact should be considered forward-looking statements,
including without limitation statements relating to events and
presentations, our product candidates, preclinical and clinical
activities, development plans, clinical safety and efficacy,
applicability across disease states, regulatory compliance, and
therapeutic impact. These forward-looking statements are based on
management's current expectations. Actual results could differ from
those projected in any forward-looking statements due to several
risk factors. Such factors include, among others, risks and
uncertainties related to our limited operating history; our
significant losses incurred since inception and expectation to
incur significant additional losses for the foreseeable future; the
development of our initial product candidates, upon which our
business is highly dependent; the impact of the COVID-19 pandemic
on our operations and clinical activities; our need for additional
funding and our cash runway; the lengthy, expensive, and uncertain
process of clinical drug development, including uncertain outcomes
of clinical trials and potential delays in regulatory approval; our
ability to maintain our relationships with our third party vendors;
and protection of our proprietary technology, intellectual property
portfolio and the confidentiality of our trade secrets. These and
other important factors discussed under the caption "Risk Factors"
in our Annual Report on Form 10-K and other filings with the U.S.
Securities and Exchange Commission could cause actual results to
differ materially from those indicated by the forward-looking
statements. Any forward-looking statements represent management's
estimates as of this date and SQZ undertakes no duty to update
these forward-looking statements, whether as a result of new
information, the occurrence of current events, or otherwise, unless
required by law.
Certain information contained in this press release relates to
or is based on studies, publications, surveys and other data
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investors@sqzbiotech.com
SQZ Biotechnologies Media Contact: John Lacey Corporate
Communications john.lacey@sqzbiotech.com 781-392-5514
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