Table 1 Summary of the current clinical development of NK cell therapies
Sponsor | Product name | NK source | Malignancy | Culture process | Clinical product development | |||
|---|---|---|---|---|---|---|---|---|
Non-engineered | Engineered | Combination Non-engineered | Combination Engineered | |||||
Acepodia | oNK cells | NK-92 | HER2 + Solid Tumors | Culture with X-VIVO 10 medium, platelet lysates and IL-2 for 6 passages | NCT04319757 | |||
Allife Medical Science and Technology | – | PB-NK | B-cell Lymphoma, Prostatic Cancer, Ovarian Cancer | No information found | NCT03690310 NCT03692767 NCT03824964 NCT03824951 NCT03692663 NCT03692637 | |||
Altor BioScience | – | PB-NK | AML | Activation with ALT-801 | NCT01478074 | |||
Artiva Biotherapeutics | – | UCB-NK | NHL | CD3- with the eFeeder technology GC Pharma) to generate a Master Cell Bank. Expanded and cryopreserved before use | NCT04673617 | |||
Asan Medical Center | – | PB-NK | NSCLC, Brain and Central Nervous System Tumors, AML, ALL, MM, MDS, Leukemias, Lymphomas, others | CD3-/CD56 + with α-MEM medium, IL-15, IL-21 and hydrocortisone for 13–20 days | NCT03366064 | NCT00823524 NCT01795378 NCT02477787 | ||
Asclepius Technology Company Group (Suzhou) | – | NK-92 | MM, Solid Tumors, Pancreatic Cancer | No information found | NCT03940833 NCT03940820 NCT03941457 NCT03931720 | |||
Beijing 302 Hospital | – | PB-NK | HCC | Culture for 14 days. No additional information found | NCT04162158 | |||
Case Comprehensive Cancer Center | – | PB-NK | AML, MDS, CML, CLL, NHL, HL, CRC, Soft Tissue Sarcoma, Ewing sarcoma, Rhabdomyosarcoma | Culture with irradiated feeder cells OCI-AML3 expressing mbIL-21 (NKF cells) and IL-2 for 3 weeks | NCT02890758 | |||
Cedars-Sinai Medical Center | – | PB-NK | MM, CLL, HL, Lymphoma | CD56 + cells. No additional information found | NCT03524235 | |||
Celularity Incorporated | CYNK-001 | UCB-CD34 | MM, AML, Leukemias, GBM, Astrocytoma, Giant Cell Glioblastoma and others | Culture with TPO, SCF, Flt3-L, IL-7, IL-15 and IL-2 for 35 days | NCT04309084 NCT04310592 NCT04489420 | |||
PNK-007 | UCB-CD34 | AML, MM | NCT02781467 NCT02955550 | NCT02955550 | ||||
Centre Hospitalier Universitaire Régional de Besançon | – | PB-NK | Gastrointestinal Cancers | CD3- cultured overnight in X-VIVO 15 medium with 10% autologous serum and IL-2 | NCT02845999 | |||
Children's Hospital Los Angeles | – | PB-NK | AML | Culture with IL-21 and irradiated feeder cells | NCT04836390 | |||
Dana-Farber Cancer Institute | – | PB-NK | AML, MDS, HNSCC | Culture with RPMI-1640 medium, 10% HS, IL-12, IL-15 and IL-18 | NCT04024761 NCT04290546 | NCT04290546 | ||
Deverra Therapeutics | DVX201 | UCB-CD34 | AML, MDS | CD34 + cultured in vessel precoated with Delta1ext-IgG (Notch ligand), serum-free medium StemSpan SFEM, IL-3, TPO, IL-6, Flt-3L, SCF for 14–16 days to generate progenitor cells. Further differentiation process not disclosed | NCT04901416 | |||
Duke University | NK-DLI | PB-NK | Myeloid and Lymphoid Malignancies | Enriched CD56 + | NCT02452697 | |||
Fate Therapeutics | FATE-NK100 | PB-NK | EGFR1 + Solid Tumors, HER2 + Gastric and Breast Cancer, Solid Tumors | No information found | NCT03319459 | |||
FT500 | iPSCs | Solid Tumors, Lymphomas | iPSCs transduced and differentiated in CD34 + hnCD16 + (18–21 days), CD34 differentiation in B0 medium with 20% HS, IL-3, IL-7, IL-15, SCF, Flt3L on EL08-1D2 stroma (culture days 28–35). NK-cells expanded using irradiated K562-mbIL21-41BBL cells and IL-2 | NCT03841110 | NCT03841110 | |||
FT596 | iPSCs | B-cell Lymphoma, CLL | NCT04245722 | NCT04245722 | ||||
FT516 | iPSCs | B-cell Lymphoma, AML, Solid Tumors | NCT04023071 NCT04551885 | NCT04023071 NCT04551885 | ||||
FT538 | iPSCs | AML, MM, Solid Tumors | NCT04614636 NCT05069935 | NCT04614636 NCT05069935 | ||||
FT576 | iPSCs | MM | NCT05182073 | NCT05182073 | ||||
Fondazione Policlinico Universitario Agostino Gemelli IRCCS | – | PB-NK | AML, MDS | Unstimulated and not expanded | NCT04166929 | NCT04166929 | ||
Fred Hutchinson Cancer Research Center | – | PB-NK | Leukemia, MDS, other Hematological Malignancies | No information found | NCT00789776 NCT00450983 | |||
Fuda Cancer Hospital | HANK | PB-NK | Liver Carcinoma, B-cell Lymphoma, Breast Cancer, NSCLC, Solid Tumors | *Culture with Human HANK Cell In Vitro Preparation and Culture Kit, serum free medium, additives (like IL-2) and irradiated K562-mbIL15-41BBL feeder layer for 12 days ^Cultured with RPMI-1640 medium, 10% FCS, IL-2 and K562-mbIL15-41BBL irradiated feeder cells for 2–3 weeks | *NCT03008343 | *NCT02843061 *NCT02843126 ^NCT02845856 *NCT02843204 *NCT02857920 | ||
GC Pharma | MG4101 | PB-NK | NHL | CD3-with CellGro SCGM serum free medium, 1% auto-plasma, anti-CD3 (OKT3), IL-2 and irradiated autologous PBMC for 14 days | NCT03778619 | |||
Glycostem Therapeutics | GTA002 | UCB-CD34 | AML | CD34 + with GBGM medium with 2–10% serum, GM-CSF, G-SCF, IL-6, SCF, Flt3L, TPO, IL-7, IL-2 and IL-15 for 42 days | NCT04632316 | |||
ImmunityBio | CD19 t-haNK | NK-92 | DLBCL | Culture with phenol-red free and gentamycin-free X-VIVO 10 medium, 5% HS and irradiated prior to infusion | NCT04052061 | |||
PD-L1 t-haNK | NK-92 | Solid Tumors, TNBC, Pancreatic Cancer, NSCLC, SCLC, HNSCC, RCC, CRC, Urothelial Carcinoma, MCC, Melanoma, Gastric Cancer, Cervical Cancer, HCC, MSI-H and dMMR Solid Tumors | NCT04050709 NCT04927884 NCT04390399 NCT03228667 | NCT04927884 NCT04390399 NCT03228667 | ||||
haNK | NK-92 | MCC, HCC, Pancreatic Cancer, SCC, CRC, TNBC, Ovarian Cancer, NSCLC, Chordoma, Malignant Neoplasm, Urothelial Carcinoma, HNSCC, NHL, MCC | NCT03853317 NCT03563170 NCT03329248 NCT03387098 NCT03586869 NCT03563144 NCT03387111 | NCT03853317 NCT03563170 NCT03329248 NCT03387098 NCT03586869 NCT03563144 NCT03387111 NCT03563157 NCT03554109 NCT03387085 NCT03197584 NCT03169777 NCT03175666 NCT03169738 NCT03574649 NCT03647423 NCT03197571 NCT03169764 NCT03169790 NCT03167164 | ||||
aNK | NK-92 | MCC, Pancreatic Cancer | NCT02465957 NCT03136406 | |||||
IRCCS Azienda Ospedaliero-Universitaria di Bologna | – | PB-NK | AML | Culture with IL-2 and feeder cells derived from 5–9 donors | NCT03955848 | |||
Johann Wolfgang Goethe University Hospital | NK-92/5.28.z or HER2.taNK | NK-92 | GBM | NK-92/5.28.z with X-VIVO 10 medium, 5% heat inactivated human plasma and IL-2. Y-irradiation with 10 Gy prior to infusion | NCT03383978 | |||
Kiadis Pharma | K-NK002 | PB-NK | AML, MDS | CD3- with feeder-free with PM21 particles for 13 days | NCT04395092 | NCT04395092 | ||
KDS-1001 | PB-NK | CML | NCT04808115 | |||||
Masonic Cancer Center, University of Minnesota | GDA-201 | PB-NK | MM, NHL, Lymphomas | CD3- with NAM and IL-15 (additional cytokines not disclosed), HS, feeder free for 14–16 days | NCT03019666 | NCT03019666 | ||
FATE-NK100 | PB-NK | Epithelial Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer, AML | CD3-/CD19- or CD3-/CD56 + in B0 mediawith 20% HS, IL-15, CHIR99021 GSK3 inhibitor and no feeder cells for 7 days | NCT03213964 NCT03081780 | ||||
FT596 | iPSCs | NHL, DLBCL, High-grade B-cell Lymphoma | iPSCs transduced and differentiated in CD34 + hnCD16 + (18–21 days), CD34 differentiation in B0 medium with 20% HS, IL-3, IL-7, IL-15, SCF, Flt3L on EL08-1D2 stroma (culture days 28–35). NK-cells expanded using irradiated K562-mbIL21-41BBL cells and IL-2 | NCT04555811 | NCT04555811 | |||
FT516 | iPSCs | Ovarian Cancer, Fallopian Tube Adenocarcinoma, Primary Peritoneal Cavity Cancer | NCT04630769 | NCT04630769 | ||||
FT538 | iPSCs | AML, Myeloid Leukemia and Monocytic Leukemia | NCT04714372 | NCT04714372 | ||||
– | PB-NK | AML | CD3-/CD19-/CD56 + cultured overnight with IL-2 | NCT01106950 | ||||
– | PB-NK | NHL or CLL | CD3- cultured with IL-2 overnight | NCT00625729 | ||||
– | PB-NK | NHL, CLL | CD3-/CD19-cultured in X-VIVO 15 with 10% HS and IL-2 | NCT01181258 | ||||
– | PB-NK | AML | CD3-/CD19- cultured overnight with ALT-803 | NCT03050216 | ||||
– | UCB-NK | Leukemia, MDS | No information found | NCT00354172 | ||||
MD Anderson Cancer Center | K-NK003 | PB-NK | AML, MDS, CML | CD3- with feeder-free with PM21 particles for 13 days | NCT05115630 | NCT05115630 | ||
– | PB-NK or UCB-NK | Myeloid Malignancies | Ex vivo expansion. No additional information found | NCT01823198 | ||||
– | PB-NK | AML, MDS, CML | CD3- with FC21 in RPMI-1640 medium with IL-2 for 14 days | NCT01904136 | ||||
– | PB-NK | Pediatric Leukemia, Lymphoma, Leukemia | No information found | NCT00941928 NCT00383994 | ||||
– | UCB-NK | Solid Tumors, B-cell Lymphoma, MDS, AML, CRC, MM, B-cell NHL, Hematological Malignances | *Culture with 45% RPMI-1640 and 45% Click’s media with 10% HS, IL-2 and IL-21 expressing-K562 (aAPC) feeder cells (clone9.mbIL21) for 14 days. CD3 depletion on day 7 before plating the cells again ^Transduced on day 6 and harvested on day 15 | *NCT03420963 | ^NCT03056339 NCT03579927 NCT05110742 NCT05092451 | NCT05040568 NCT02280525 NCT01619761 NCT03019640 NCT01729091 | NCT03579927 | |
AFM13-NK | UCB-NK | HL, NHL | CD56 + with IL-2 and irradiated K562 (clone 9.mbIL21) feeder cells | NCT04074746 | ||||
– | NK-92 | MDS, Leukemia, Lymphoma, MM | No information found | NCT02727803 | ||||
Medical College of Wisconsin | – | PB-NK | Sarcomas | No information found | NCT02100891 | |||
Memorial Sloan Kettering Cancer Center | – | PB-NK | Neuroblastoma | CD3-/CD56 + cultured with IL-2 overnight | NCT00877110 NCT02650648 | |||
Miltenyi Biotech | – | PB-NK | AML | CD3-/CD19- or CD3-/CD56 + . No additional information found | NCT03152526 | |||
Nanfang Hospital of Southern Medical University | – | UCB-NK | HCC | No information found | NCT05171309 | |||
National Cancer Institute | PD-L1 t-haNK | NK-92 | GEJ Cancers, HNSCC | Culture with phenol-red free and gentamycin-free X-VIVO 10 medium, 5% HS and co-irradiated prior to infusion | NCT04847466 | NCT04847466 | ||
– | PB-NK | Leukemia, Lymphoma | Culture with K562-mbIL15-41BBL and IL-15 | NCT01287104 | ||||
National University Health System Singapore | – | PB-NK | B-ALL, Neuroblastoma | Cultured with K562-mb15-4-1BBL *(with IL-2 and then transduced) | *NCT01974479 | NCT03242603 | ||
Nkarta Therapeutics | NKX101-101 | PB-NK | AML, MDS | Culture with stimulatory cells, transduced and expanded with mbIL-15 | NCT04623944 | |||
NKX019 | PB-NK | NHL, CLL, B-ALL | NCT05020678 | |||||
Ohio State University Comprehensive Cancer Center | K-NK003 | PB-NK | AML, MDS | CD3- with FC21 mbIL21 feeder cells for 13 days | NCT04220684 | |||
– | PB-NK | T cell Leukemia/Lymphoma | Culture with NK cell expansion medium, IL-2 from day 3, irradiated K562 Cl9 mIL21 (CSTX002) feeder cells for 21 days | NCT04848064 | ||||
PersonGen BioTherapeutics | – | NK-92 | Solid Tumors, AML, Leukemias, Lymphomas, | No information found | NCT02839954 NCT02944162 NCT02742727 | |||
PCAR-119 | NK-92 | B-cell Lymphoma, Leukemia | No information found | NCT02892695 | ||||
Precision Biotech Taiwan Corp | PB103 | PB-NK | NSCLC | Culture with DMEM-F12, ultraGRO, RPMI-1640 or SCGM media, without serum, with IL-2, heparin, anti-CD3 mAb for 10–16 days | NCT04616209 | |||
Radboud University | – | UCB-CD34 | AML, Ovarian Cancer, Fallopian tube or Primary Peritoneal Carcinoma | CD34 + culture process includes StemRegenin 1, GM-CSF, G-SCF, IL-6, SCF, Flt3L, TPO, IL-7, IL-2 and IL-15, 10% HS for 42 days | NCT04347616 NCT03539406 | |||
Royan Institute | – | PB-NK | GBM | Culture with RPMI-1640 medium, IL-2 and HSP70 for 16 days | NCT05108012 | |||
Samsung Medical center | – | PB-NK | Neuroblastoma, Soft Tissue Sarcomas and Osteosarcomas | No information found | NCT01807468 | |||
Seoul National University Hospital | MG4101 | PB-NK | AML | CD3- with CellGro SCGM serum free medium, 1% auto-plasma, anti-CD3 (OKT3), IL-2 and irradiated autologous PBMCs for 14 days | NCT03349502 | |||
Shandong Golden Brick Biotechnology | – | UCB-NK | Advanced Gastric Cancer | No information found | NCT04385641 | |||
Shanghai East Hospital | – | Unknown | Solid Tumors | No information found | NCT05137275 | |||
Shanghai iCELL Biotechnology | PB-NK | AML | No information found | NCT04209712 | ||||
SMT bio | SMT-NK | PB-NK | BTC | No information found | NCT03937895 | |||
St. Jude Children's Research Hospital | – | PB-NK | B-ALL, Leukemia, Lymphoma | *CD3- hematopoietic progenitor cells CD34 + CD45RA- | NCT00995137 | *NCT01807611 NCT01621477 NCT01576692 | ||
– | PB-NK | Pediatric AML, ALL, CML, MDS, Histiocytosis, Neuroblastoma, Lymphoma, High-risk Tumors | CD3-/CD56 + infused fresh *(less than 12 h process) | *NCT00145626 *NCT02130869 | ||||
– | PB-NK | Pediatric Neuroblastoma | NCT01857934 | |||||
Takeda | TAK-007 | UCB-NK | B-cell NHL, NHL | No information found | NCT05020015 | |||
The Third Affiliated Hospital of Guangzhou Medical University | – | PB-NK | Metastatic Solid Tumors | Culture with NK cell growth medium with 1% HS and IL-2 | NCT03415100 | |||
University Hospital, Basel, Switzerland | – | PB-NK | AML, MDS | CD3-/CD56 + with SCGM medium, 5% HS, IL-2, IL-15, fresh anti-CD3 every day and irradiated autologous feeder cells for 19–20 days | NCT03300492 | |||
University of Arkansas | – | PB-NK | MM | Culture with K562 mIL15/4-1BBL | NCT01313897 | |||
University of Wisconsin | EANK | PB-NK | Neuroblastoma, Osteosarcoma | Culture with K562-mbIL15-41BBL | NCT03209869 | |||
Washington University School of Medicine | WU-NK-101 | PB-NK | AML, MDS | Culture with RPMI-1640 medium, 10% HS, no feeder cells for 14 days. Activation with heteromeric fusion protein complex IL-12, IL-15, IL-18 (WU-PRIME) for 12-16 h | NCT04893915 | |||
– | PB-NK | AML, MDS | *CD3-/CD56 + with IL-2, IL-15 and IL-18 for 12 h | NCT04354025 | *NCT01898793 | |||
Wuhan Union Hospital | – | UCB-NK | NHL, CLL | No information found | NCT04796675 | |||
Xinqiao Hospital of Chongqing | UCB-NK | MM | No information found | NCT05008536 | ||||
– | Unknown | NHL, AML | No information found | NCT04639739 NCT05008575 | ||||
Xinxiang Medical University | – | NK-92 | NSCLC | No information found | NCT03656705 | |||
Yonsei University | – | PB-NK | BTC | ALyS505NK-IL2 for 21 days | NCT03358849 | |||