SQZ Biotechnologies Presents Preclinical SQZ® TIL Data Supporting Potential Ability of mRNA-Driven IL-2 and IL-12 Expression to Eliminate Need for Toxic Preconditioning and Systemic IL-2 Administration for Certain T Cell Therapies
12 Setembro 2022 - 7:00AM
Business Wire
TILs Engineered to Temporarily Express
Membrane-Bound IL-2 and IL-12 Could Potentially Improve TIL
Function While Simultaneously Eliminating the Need for Toxic
Preconditioning and Cytokine Administration
Data Presented at ESMO 2022 Show SQZ® TILs
Enhanced Proliferation In Vitro and In Vivo, Increased Tumor Cell
Killing, and Upregulated Markers Associated with T Cell Memory
SQZ® TILs May Enable Repeat Dosing and Early
Line Use of TIL Therapy in Oncology
SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking
the full potential of cell therapies for multiple therapeutic
areas, today presented preclinical data supporting that tumor
infiltrating lymphocytes (TILs) engineered with membrane-bound
cytokines IL-2 (mbIL-2) and IL-12 (mbIL-12) may eliminate the need
for the high-dose, systemic IL-2 and lymphodepleting
preconditioning used with current TIL therapies. SQZ® TILs showed
the ability to induce desirable cytokine signaling for more than 48
hours, which is comparable to the duration of exogenous IL-2
support in current TIL therapies. SQZ® TILs also demonstrated
improved killing of donor-matched tumor cells, upregulated markers
associated with central memory T cells, and persistence in vivo.
The data was presented today at the European Society for Medical
Oncology (ESMO) Congress 2022.
“TIL therapies have shown exciting clinical results in solid
tumors, but to overcome engraftment and persistence challenges they
also require lymphodepletion and systemic IL-2, which are toxic to
patients and prevent repeat dosing,” said Jonathan Gilbert, Ph.D.,
Vice President of Exploratory Research at SQZ Biotechnologies. “By
providing cytokine support on the surface of the cell, SQZ® TILs
may simultaneously eliminate the need for these toxic co-treatments
and improve T cell function. Together this could potentially
increase potency while also moving TILs to an outpatient procedure
that allows repeat dosing and combination therapies.”
The SQZ® TIL platform draws from the company’s mbIL-2 and
mbIL-12 constructs used in its enhanced Antigen Presenting Cell
(eAPC) clinical trial. Both approaches are designed to take
advantage of transient expression of membrane-bound cytokines so
that potent cytokines such as IL-12 can be expressed without
systemic toxicities. Additional TIL engineering with membrane-bound
IL-7 (mbIL-7) and BCL-2, an anti-apoptotic factor, may further
enhance the abilities of SQZ® TILs to engraft without
preconditioning.
Major Findings from Preclinical
Research
Poster #761: Tumor Infiltrating Lymphocytes Expressing
Membrane-Bound IL-2 and IL-12 Exhibit Enhanced Proliferation,
Function, and Persistence Without Requiring Exogenous IL-2
Support
- Cytokine Expression and Function: TILs engineered with
mbIL-2 and mbIL-12 induced high levels of expression and supported
>70% viability in the absence of external cytokine support for 5
days, a time greater than IL-2 is typically dosed in the clinic
after TIL infusion. The membrane-bound cytokines produced an almost
4-fold expansion in vitro, which was comparable to unmodified TILs
cultured in IL-2 containing media
- Tumor Cell Killing: TILs from primary solid tumors
engineered with mbIL-2 and mbIL-12 and subsequently cultured with
donor-matched tumor cell lines showed 3.5-fold higher IFN-y release
than the current clinical standard of unmodified TILs with
exogenous IL-2, as well as increased tumor killing as measured by
staining of apoptotic cells
- Memory T Cell Reprogramming: TILs engineered to express
mbIL-2 and mbIL-12 upregulated CD62L, a classical marker of central
memory T cells (>80% positive, vs <20% positive for
unmodified TILs at day 6). CD62L remains upregulated even after
cytokine expression has diminished, suggesting a potential
reprogramming of the TILs to a more memory-like state, which could
positively impact T cell survival and clinical benefit
- In Vivo Survival and Phenotype: mbIL-2 and mbIL-2/12
TILs adoptively transferred into a mouse model each showed more
than 200% greater cell persistence in vivo as compared to
unmodified TILs, and mbIL-12 drove a 3.5-fold enrichment in CD62L
expression in vivo out to at least day 5 post-transfer
- Promising Targets: TILs engineered with mbIL-7 and BCL2,
which can support cell survival, demonstrated a strong advantage in
the absence of exogenous cytokine support and could serve as
potential future TIL enhancers
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, platform and
clinical development, product candidates, preclinical and clinical
activities, progress and outcomes, development plans, clinical
safety and efficacy results, and therapeutic potential. 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
obtained from third-party sources and our own internal estimates
and research. While we believe these third-party sources to be
reliable as of the date of this press release, we have not
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version on businesswire.com: https://www.businesswire.com/news/home/20220912005138/en/
Media: Erin Phelps erin.phelps@sqzbiotech.com
857-760-0920 Investor: Mike Kaiser
michael.kaiser@sqzbiotech.com 857-760-0398
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