Table 3.
List of biotech NK cellular therapies and NK cell function enhancing compounds.
| Company | NK cell product | Product characteristics | Disease target | Product stage |
|---|---|---|---|---|
| Fortress Biotech Inc. | CNDO-109 | Tumor primed NK cells | AML | Phase I/II |
| Multimmune GmbH | ENKASTIM-ev | A synthetic peptide which mimics Hsp70 and activates NK cells ex vivo | Metastatic colon and non-small cell lung cancer | Phase II |
| Glycostem Therapeutics | oNKord® | NK cells derived from umbilical cord blood (UCB) progenitor cells | AML and solid tumors | Phase I (AML) |
| NantKwest Inc. | Activated NK-92 cells (aNK cell) | IL-2-dependent tumor cell-derived NK cell line | Solid tumors and hematological malignancies | Phase I |
| High affinity NK cells (haNK) | aNK cells genetically modified to express CD16 for ADCC with therapeutic mAbs | Ideally in combination with IgG1 therapeutic mAbs in solid tumors (e.g., cetuximab) and hematological malignancies (e.g., rituximab) | Preclinical | |
| Target-activated NK cells (taNK) | aNK cells genetically modified to express CARs | NK-92 CARs are developed targeting tumor antigens in neuroblastoma, melanoma, breast cancer, MM and leukemias | Preclinical | |
| Green Cross Lab Cell | MG4101 | Ex vivo expanded NK cells derived from CD3 depleted unrelated donors | Solid tumors and lymphoma (NCT01212341) | Phase I |
| Gamida Cell | NAM-NK cells | Nicotinamide-based PBNK cell culture system | Solid tumors and hematological malignancies | Preclinical |
| Celgene Cellular Therapeutics | NK cells | NK cells derived from UCB and placenta. | Solid tumors and hematological malignancies | Preclinical |
| Fate Therapeutics Inc. | iNK cells | NK cells derived from induced pluripotent stem cells | Solid tumors and hematological malignancies | Preclinical |
| Sorrento Therapeutics Inc | CARs to enhance tumor homing of NK-92 cells | NK-92 cells CAR targeting programming death ligand-1 and NK-92 CAR targeting receptor tyrosine kinase like orphan receptor to increase NK-92 tumor homing | Solid tumors and hematological malignancies | Preclinical |
| Nkarta Therapeutics | NKG2D CARs | NKG2D CARs developed with NK-92 and PBNK to enhance the functions of NKG2D receptor in NK cells | Osteosarcoma and hepatocellular carcinoma | Preclinical |
| Ziopharm Oncology Inc. | HLA gene editing | Zinc finger nuclease technology to delete HLA-A sequences from allogeneic NK cells, allowing them to evade recipient T cell killing | Solid tumors and hematological malignancies | Preclinical |
| Company | NK cell enhancing products | Product characteristics | Disease target | Product stage |
| Kyowa Hakko Kirin | Mogamulizumab | Fc optimized anti CCR4 CD20 mAb | CTCL | Phase III |
| Genentech | Obinutuzumab | Fc optimized anti CD20 mAb | CLL | Phase II |
| Mentrik Biotech, LLC | Ocaratuzumab | Fc optimized anti CD20 mAb | CLL | Phase II |
| Roche Glycart | Imgatuzumab | Fc optimized anti EGFR mAb | Head and neck and KRAS mutant colorectal cancer | Phase I/II |
| Affimed N.V. | AFM13 | Bispecific antibody binding to CD16a on NK cells and CD30 on tumor cells | Hodgkin’s lymphoma and lymphomas | Phase II |
| AFM22 | Bispecific antibody binding to CD16a on NK cells and EGFR vIII on tumor cells | Head and neck and solid tumors | Preclinical | |
| AFM24 | Bispecific antibody binding to CD16a on NK cells and wild type EGFR on tumor cells | EGFR-expressing solid tumors | Preclinical | |
| Innate Pharma S. A. | Lirilumab | mAb to block NK cell inhibitory signaling from KIRs (KIR2DL1–3) | As monotherapy (Phase II, NCT02399917), with nivolumab (Phase I, NCT01592370), with ipililumab (Phase I, NCT01750580), 5-azacytidine (Phase I, NCT02399917), with nivolumab + 5-azacytidine (Phase II, NCT02599649), with elotuzumab (NCT02252263) and with rituximab (Phase I, NCT02481297) | Phase I/II |
| Innate Pharma S. A. | Monalizumab | mAb to block NK cell inhibitory receptor NKG2A | As monotherapy (Phase I/II, NCT02459301, NCT02331875) with cetuximab (NCT02643550), with ibrutinib (NCT02557516) and with durvalumab (NCT02671435) | Phase I/II |
| IPH4102 | mAb to block NK cell inhibitory receptor KIR3DL2 | As monotherapy in CTCL (NCT02593045) | Phase I | |
| IPH4301 | mAb to target NKG2D ligands MICA/MICB and it also mediates ADCC with NK cells | Solid tumors and hematological malignancies | Preclinical | |
| Altor Biosciences corporation | ALT-803 | IL-15 super agonist reported to stably express IL-15. Increases NK cell proliferation in vivo, also enhances expansion of migratory NK subsets | Advanced solid tumors (NCT01946789), MM (NCT02099539), HIV patients (NCT02191098), with nivolumab in NSCLC (NCT02523469), with rituximab (NCT02384954) in B cell Non-Hodgkin Lymphoma (NHL) (NCT02384954), with (BCG) in Non-Muscle Invasive Bladder Cancer (NCT02138734), with chemotherapy drugs gemcitabine and Nab-paclitaxel in advanced pancreatic cancer (NCT02559674) | Phase I/II |
| NOXXON Pharma | NOX-A12 | Functions as chemokine receptor CXCL12 inhibitor, enables the release of CXCL12 from the surface of tumor stromal cells, thus facilitating migration of tumor cells toward NK cells | Solid tumors and MM | Preclinical |
| AvidBiotics | MicAbody proteins | Dual role: binds to NKG2D receptor in NK cells and to target antigens of interest simultaneously | Solid tumors and hematological malignancies | Preclinical |
KIRs, killer cell immunoglobulin-like receptors; ADCC, antibody-dependent cell mediated cytotoxicity; aNK, activated NK cells; haNK, high affinity NK cells; taNK, target activated NK cells; mAbs, monoclonal antibodies; NAM, nicotinamide; CARs, chimeric antigen receptors; EpCAM, epithelial cell adhesion molecule; AML, acute myeloid leukemia; KIR2DL1–3, killer cell immunoglobulin like receptor two domains long cytoplasmic tail 1–3; KIR3DL2, killer cell immunoglobulin like receptor three domains long cytoplasmic tail 2; MICA/MICB, MHC class-I-chain related protein A and B; HIV, human immunodeficiency virus; NSCLC, non-small-cell lung cancer; BCG, Bacillus Calmette Guerin; MM, multiple myeloma; CLL, chronic lymphocytic leukemia; CTCL, cutaneous T cell lymphoma; EGFR, epidermal growth factor receptor.