NantKwest Announces Studies in Collaboration with the National Cancer Institute Demonstrating Enhanced Killing Activity of ...
10 6월 2020 - 10:00PM
Business Wire
- NantKwest’s antibody-targeted NK cell line, haNK, which
is engineered for increased antibody-dependent cell-mediated
cytotoxicity and activation, showed increased resistance to hypoxic
conditions as seen in suppressive tumor microenvironments
- NantKwest’s PD-L1 t-haNK cells, haNK cells engineered to
express PD-L1 checkpoint-directed chimeric antigen receptors,
demonstrated in-vivo tumor trafficking, significant elimination of
both monocytic and granulocytic MDSCs and demonstrated robust
anti-tumor activity in cancer cell lines and in mouse models
- Studies demonstrated the ability of PD-L1 t-haNK to kill 20 out
of 20 human cancer cell lines tested, including triple negative
breast cancer (TNBC) and lung, urogenital, and gastric cancer
cells
NantKwest, Inc. (Nasdaq: NK), a clinical-stage, natural killer
cell-based therapeutics company, today announced the publication of
two peer-reviewed manuscripts in the Journal of Immunotherapy of
Cancer. These invitro and in-vivo studies, conducted in
collaboration with the National Cancer Institute pursuant to a
Cooperative Research and Development Agreement, support the
mechanism and functionality of NantKwest’s clinical-stage
engineered natural killer (NK) cell lines, haNK® and first-in-class
PD-L1 t-haNKTM, as effecting anti-tumor activity in
treatment-refractory cancer types even in the hypoxemic setting of
the solid tumor microenvironment.
“These published studies provide important insight and
validation for the mechanism and activity of our novel
first-in-class engineered NK cells for use in notoriously difficult
solid tumor types,” said Patrick Soon-Shiong, M.D., Chairman and
Chief Executive Officer of NantKwest. “NK cells have the potential
to kill tumor cells; however, the hypoxic nature of the suppressive
tumor environment has been shown to curb primary NK cell function.
These published data indicate that our engineered haNK cells remain
active in hypoxic conditions, which may be an important new
mechanism of its anti-tumor activity. In addition, our NK cells
appear to be resistant even to acute hypoxia and are capable of
maintaining tumor killing activity in conditions comparable to a
suppressive tumor microenvironment.”
Dr. Soon-Shiong continued, “In addition, we are encouraged to
observe anti-tumor activity in every cancer cell line tested by the
investigators at NCI. The positive data in the in-vivo models of
solid tumors with PD-L1 t-haNK, our engineered haNK cell line that
also expresses a PD-L1 CAR, provides a novel approach to target
tumors expressing PD-L1. This highly targeted NK cell therapy has
the potential to address the evolution of tumors as they become
resistant to chemotherapy, antibody therapy and, ultimately,
checkpoint immunotherapy. We have hypothesized that cancer
undergoes a quantum change and adapts to the therapy administered,
resulting in the selection of resistant, cancer stem-like cells. It
is at this stage of evolution where intractable tumors such as in
patients with metastatic pancreatic cancer and triple negative
breast cancer, are deemed incurable. It is our belief that these
cancer “stem” cells, which do not divide and hence are untouchable
by chemotherapy, become resistant and render checkpoint therapy
futile by not expressing t-cell receptor ligands. In the face of
this immunosuppressive milieu, our PD-L1 t-haNK cells can act to
kill these otherwise highly resistant cancer cells, as demonstrated
by these two important reports by our colleagues at the NCI. Our
clinical results in the first patient with advanced metastatic
pancreatic cancer to have received PD-L1 t-haNK demonstrated a
durable complete response.”
Study highlights from the publication titled “Overcoming
hypoxia-induced functional suppression of NK cells” include:
- NantKwest haNK cells engineered to express a high-affinity CD16
receptor as well as internal interleukin (IL)-2 for increased
antibody-dependent cellular cytotoxicity (ADCC) and activation
maintained killing activity under hypoxic conditions comparable to
those of the suppressive tumor microenvironment, while healthy
donor NK cell activity was significantly impaired
- NK killing, serial killing and ADCC were maintained under
hypoxia in haNK cells
- haNK cells’ IL-2 is likely a driver of maintained killing
capacity under hypoxic conditions
Study highlights from the article titled “PD-L1-targeting
high-affinity NK cells (PD-L1 t-haNK) induce direct antitumor
effects and target suppressive MDSC populations” include:
- PD-L1.t-haNK cells engineered to express a high-affinity CD16
receptor, an internal interleukin (IL)-2 and PD-L1-specific
chimeric antigen receptor (CAR) broke down all 15 human tumor cell
lines tested, including those modelling historically
treatment-refractory cancers (triple negative breast cancer, lung,
and urogenital cancer)
- In vitro, the cytotoxicity of PD-L1 t-haNK cells was correlated
to the PD-L1 expression of the tumor targets
- In mouse models of solid tumors, PD-L1 t-haNK inhibited the
growth of engrafted TNBC, lung and bladder tumors in mice without
toxicity
The articles may be found on the Publications section of the
NantKwest corporate website here:
https://nantkwest.com/peer-reviewed-publications/
About NantKwest NantKwest (NASDAQ: NK) is an innovative,
clinical-stage immunotherapy company focused on harnessing the
power of the innate immune system to treat cancer and
virally-induced infectious diseases. NantKwest is the leading
producer of clinical dose forms of off-the-shelf natural killer
(NK) cell therapies. The activated NK cell platform is designed to
destroy cancer and virally-infected cells. The safety of these
optimized activated NK cells—as well as their activity against a
broad range of cancers—has been tested in Phase I clinical trials
in Canada and Europe, as well as in multiple Phase I and II
clinical trials in the United States. By leveraging an integrated
and extensive genomics and transcriptomics discovery and
development engine, together with a pipeline of multiple,
clinical-stage, immuno-oncology programs, NantKwest’s goal is to
transform medicine by delivering off-the-shelf, novel NK cell-based
therapies to routine clinical care. NantKwest is a member of the
NantWorks ecosystem of companies. For more information, please
visit www.nantkwest.com.
haNK is a registered trademark of NantKwest, Inc.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements include statements concerning or
implying that NantKwest will be successful in improving the
treatment of cancer or other critical illnesses, including
COVID-19. Risks and uncertainties related to these endeavors
include, but are not limited to, obtaining FDA approval of
NantKwest’s NK cells as well as other therapeutics and
manufacturing challenges.
Forward-looking statements are based on management’s current
expectations and are subject to various risks and uncertainties
that could cause actual results to differ materially and adversely
from those expressed or implied by such forward-looking statements.
Accordingly, these forward-looking statements do not constitute
guarantees of future performance, and you are cautioned not to
place undue reliance on these forward-looking statements.
These and other risks regarding NantKwest’s business are
described in detail in its Securities and Exchange Commission
filings, including in NantKwest’s Quarterly Report on Form 10-Q for
the quarter ended March 31, 2020. These forward-looking statements
speak only as of the date hereof, and we disclaim any obligation to
update these statements except as may be required by law.
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Jen Hodson NANT Jen@nant.com
NantKwest (NASDAQ:NK)
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