First engineered, GMP-grade, cryopreserved, off-the-shelf, bi-specific NK cell therapy to enter human clinical trials targeting PD-L1 and CD16 in patients with solid tumors
Programmed death-ligand 1 (PD-L1) is a transmembrane protein that plays a major role in suppressing the immune system in many cancer patients. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 establishes an inhibitory signal that reduces the proliferation of antigen-specific T-cells while also reducing apoptosis in suppressive regulatory T cells (Tregs) that further inhibits immune responses.
NantKwest’s PD-L1 t-haNK cell therapy is a novel, NK cell-based immuno-oncology therapy that includes a PD-L1 based Chimeric Antigen Receptor (CAR) engineered into the company’s proprietary haNK NK cell, which also includes the high affinity variant of the CD16 receptor (V158 FcγRIIIa) to mediate antibody dependent cellular cytotoxicity (ADCC). Together, the use of this targeted, bi-specific, next generation PD-L1 t-haNK therapy has been shown in preclinical studies to significantly enhance cancer cell killing and improve overall response rates.
“In just a few short weeks since announcing the
NantKwest’s PD-L1 t-haNK cell therapy is designed to provide precise tumor-cell specificity through the use of a CAR construct that utilizes a PD-L1-specific scFv (single chain antibody fragment) engineered into the company’s proprietary haNK NK cell that includes the high affinity variant of the CD16 receptor (V158 FcγRIIIa) to mediate antibody dependent cellular cytotoxicity (ADCC). In preclinical studies, cytotoxicity of these GMP-grade, cryopreserved PD-L1 t-haNK cells were comprehensively evaluated against a panel of cancer cell lines with different levels of PD-L1 expression in vitro and in vivo, with these studies showing increased activity and selective cytotoxicity toward a wide range of PD-L1-expressing tumor cells.
To better inform routine patient care, these clinical trials will incorporate a state-of-the-art, biomarker analysis, including GPS Cancer™, which is an integrated, multi-omics, whole genome, transcriptomic platform, 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
NK-92, aNK, haNK, taNK, and t-haNK are trademarks of
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