Unum Therapeutics Presents Preclinical Data for BOXR1030 at the Society for Immunotherapy of Cancer (SITC) Annual Meeting
November 05 2019 - 8:30AM
Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage
biopharmaceutical company focused on developing curative cell
therapies for cancer, today announced preclinical data for its
BOXR1030 program presented at the SITC meeting being held November
6–10, 2019 in National Harbor, MD.
“Solid tumors create an unfavorable
microenvironment that depletes T cells of critical nutrients and
amino acids, drives T cell dysfunction, and inhibits the
effectiveness of cellular therapies, and our BOXR platform was
specifically developed to discover novel transgenes that can be
co-expressed with chimeric-targeting receptors to improve T cell
functionality in the solid tumor microenvironment,” said Seth
Ettenberg, Ph.D., Chief Scientific Officer of Unum. “At this year’s
SITC, we present preclinical data on the first product candidate
from our BOXR platform, BOXR1030, which contains the GOT2
transgene. In our preclinical studies using stringent animal
xenograft models that simulate the solid tumor microenvironment,
expression of the GOT2 mitochondrial enzyme in BOXR1030 increased
the production of key amino acids and metabolites, improved the
anti-oxidant balance of T cells, and prevented their dysfunction
and exhaustion. This work extends the increasingly recognized
importance of immunometabolism in ensuring proper immune cell
function.”
Poster presentation title: “Co-expression of the
Metabolic Enzyme GOT2 with a GPC3-Targeted CAR-T Overcomes
Challenges of the Solid Tumor Microenvironment, Substantially
Improving Therapeutic Efficacy in Solid Tumor Xenografts”
BOXR1030 Summary:
- BOXR1030 contains a humanized single-chain variable fragment
(scFv) 4-1BB CAR targeting GPC3 and separately co-expresses the
glutamic-oxaloacetic transaminase 2 (GOT2) transgene from a single
viral construct. Unum’s BOXR platform led to the discovery of the
utility of GOT2, a critical enzyme involved in cellular metabolism.
When co-expressed with a GPC3-targeted CAR-T, GOT2 improved
metabolic and transcriptional profiles resulted in greater
anti-tumor activity compared with parental CAR-T when tested both
in vitro and in vivo under stringent conditions representing the
solid tumor microenvironment (TME).
- Over one hundred BOXR candidates were generated by cloning a
library of literature-derived, hypothesis-driven bolt-on genes into
vectors containing a GPC3-targeted CAR-T and were screened through
Unum’s novel TME assays. Candidates were selected for their ability
to overcome multiple TME challenges, while maintaining specificity
and tolerability.
- In vitro, BOXR1030 T cells were resistant to suppressive
TME-like conditions, showing improved T cell proliferation under
both hypoxic and low glucose conditions compared with control GPC3+
CAR-T cells. In vivo, BOXR1030 demonstrated superior activity
compared to the parental CAR-T with treated animals achieving
complete tumor regressions. Tumor infiltrating lymphocytes isolated
from the tumors of treated animals revealed that BOXR1030 cells
were more resistant to dysfunction and had fewer markers of
exhaustion as compared to the control CAR-T cells.
About
Unum’s BOXR platform Unum's BOXR platform was established
with the aim of discovering novel “bolt-on” transgenes that can be
co-expressed with chimeric-targeting receptors to improve the
function of T cells in the solid tumor microenvironment. Unum’s
BOXR discovery capabilities broadly evaluate T cell phenotype
through a rigorous, multi-stage screening strategy that simulates
the tumor microenvironment. Unum has discovered and continues to
enrich a library of master regulatory genes of T cell biology that
regulate pathways essential for cell growth, proliferation, and
survival under a variety of conditions. BOXR bolt-on transgenes
identified in this platform are designed to address a variety of
immunosuppressive mechanisms of solid tumors, including metabolic
competition, immune suppressor cells, and exhaustion due to chronic
stimulation. Once discovered, BOXR transgenes are designed to be
incorporated into several different types of therapeutic T cells,
including both ACTR T cells and CAR-T cells, to impart new
functionality to T cells. BOXR platform objectives include
expanding the scope of biological mechanisms and transgenes in its
proprietary BOXR library, enabling BOXR bolt-on applications for a
broad range of immune cell therapies, including both autologous and
allogeneic approaches, and advancing new BOXR product candidates
into the clinic.
About Unum Therapeutics
Unum Therapeutics is a clinical-stage
biopharmaceutical company focused on developing curative cell
therapies to treat a broad range of cancer patients. Unum’s novel
proprietary technologies include Antibody-Coupled T cell Receptor
(ACTR), an autologous engineered T-cell therapy that combines the
cell-killing ability of T cells and the tumor-targeting ability of
co-administered antibodies to exert potent antitumor immune
responses, and Bolt-On Chimeric Receptor (BOXR), designed to
improve the functionality of engineered T cells by incorporating a
“bolt-on” transgene to overcome resistance of the solid tumor
microenvironment to T cell attack. Unum has multiple programs in
Phase 1 clinical testing and preclinical testing, including;
ACTR707 used in combination with trastuzumab in adult patients with
HER2+ advanced cancer and used in combination with rituximab in
adult patients with r/r NHL; and BOXR1030 targeting GPC3+ solid
tumor cancers. The Company is headquartered in Cambridge, MA.
Follow Unum Therapeutics on social media:
@UnumRx, and LinkedIn.
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activities, the development of our product candidates, including
the BOXR platform and product candidates, and the anticipated
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Investor Contact: Stern Investor Relations, Inc. Stephanie
Ascher, 212-362-1200 stephanie@sternir.com
Media Contact:Lissette Steele,
202-930-4762lsteele@vergescientific.com
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