First engineered, GMP-grade, cryopreserved, off-the-shelf, bi-specific NK cell therapy to enter human clinical trials targeting CD16 and CD19 in patients with lymphoma
CD19 is a transmembrane protein expressed in B cells and overexpressed in a large percentage of advanced leukemia and lymphoma representing a well validated therapeutic target. The CD19 t-haNK cell therapy is a novel, NK cell based immuno-oncology therapy that includes a CD19-based Chimeric Antigen Receptor (CAR) that has been engineered to create an NK cell that includes the high affinity CD16 (Fc receptor), which enhances an NK cell’s ability to bind and enhance monoclonal antibody activity. Use of a targeted, bi-specific NK cell is intended to enhance the cancer cell killing ability of this novel NK cell therapy.
“Based on extensive and encouraging preclinical results, we have
enhanced our ability to modularly combine this proprietary off-the-shelf
t-haNK-based therapy with a wide range of monoclonal antibodies using
this multi-targeted approach,” commented Dr.
NantKwest’s CD19-t-haNK cell therapy is designed to provide precise tumor-cell specificity through the use of a CAR construct that utilizes a CD19-specific scFv (single chain antibody fragment) engineered into the company’s proprietary NK cell that includes the CD16 (Fc high affinity receptor).
In pre-clinical studies, cytotoxicity of these GMP-grade, cryopreserved CD19 t-haNK cells were comprehensively evaluated against a panel of cancer cell lines with different levels of CD19 expression in vitro and in vivo, with these studies showing increased activity and selective cytotoxicity towards CD19-expressing tumor cells of various b-cell origins including leukemia.
To better inform routine patient care, these clinical trials will
incorporate a state-of-the-art, biomarker analysis using GPS Cancer™,
which is an integrated, multi-omics, whole genome, transcriptomic
platform, both provided by
With the capacity to grow active killer cells as a cancer therapy, our NK cells have been designed to induce cell death against cancers and virally infected cells by several mechanisms, including: (i) innate killing, whereby all of our NK platforms recognize the stress proteins typically found on cancer cells, which, upon binding, release toxic granules to immediately kill their targets; (ii) antibody-mediated killing with our haNK® platform, which are NK cells engineered to express antibody receptors that can bind to therapeutic antibody products, thereby enhancing the cancer cell killing effect of that antibody; and (iii) Chimeric Antigen Receptor directed killing using the taNK® platform, which includes NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells. All three modes of killing (innate, antibody-mediated, and CAR directed killing) are employed by our t-haNK™ platform, which is an innovative combination of our aNK, haNK® and taNK® platforms in a single product.
Our haNK®, and t-haNK™ platforms have been designed to address certain
limitations of CAR T-cell therapy including the capability to infuse
cell therapy in an outpatient setting which allows for potential
reduction of risk for serious cytokine storms and protracted serious
adverse events. In Phase I and II clinical trials in patients with late
stage cancer, our NK cells have been administered as an investigational
outpatient infusion safely with greater than 500 infusions to date at a
dose of 2 billion cells per infusion. By leveraging an
integrated and extensive genomics and transcriptomics discovery and
development engine, together with a pipeline of multiple,
clinical-stage, immuno-oncology programs, we believe
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
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