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. 2022 Mar 8;23(3):381–403. doi: 10.1007/s11864-021-00932-2

Table 4.

Preclinical studies of human NK therapy for lymphoma

NK source Activation and expansion method Genetically engineered Engineering method Combination Lymphoma subtype Study stage Year Ref
NK-92 IL-2 No N/A Human BL Preclinical 1994 [59]
haNK N/A Yes (CD16-158V and erIL2) Transfection/insertion rituximab Human CD20+ lymphoma Preclinical 2016 [60]
CB Anti-CD3, IL2, IL7, IL12 No No N/A Human BL Preclinical 2009 [64]
hESC NK differentiation medium (IL15, IL3, IL7, SCF, Flt3L) and irradiated AFT-24 cells No No rituximab Human BL Preclinical 2005 [67]
iPSC N/A Yes (ADAM17 knockdown) CRISPR/Cas9 rituximab Human BL Preclinical 2020 [69]
PB IL12, IL15, IL18 No No rituximab Human BL Preclinical 2017 [8890]
PB NAM, IL2, IL15 No No No Human BL Preclinical 2011 [79]
PB irradiated autologous PBMCs No No No Human BL Preclinical 2013, 2013, 2017 [7173]
PB irradiated k562-mbIL15-41BBL No No No Human BL Preclinical 2013 [77]
CB irradiated k562-mbIL15-41BBL No No No Human BL DLBCL Preclinical 2017 [76]
PB irradiated k562-mbIL21-41BBL No No No Human BL Preclinical 2012 [78]
PB irradiated k562-mbIL15-41BBL Yes (anti-CD19 CAR) mRNA electroporation No Human BL Preclinical 2012 [83]
PB irradiated k562-mbIL15-41BBL Yes (anti-CD20 CAR) mRNA electroporation No rituximab sensitive and resistant human BL Preclinical 2015 [84]
PB irradiated k562-mbIL15-41BBL Yes (anti-CD20 CAR) mRNA electroporation romidepsin rituximab sensitive and resistant human BL Preclinical 2017 [85]
NK-92 IL2 Yes (anti-CD19 CAR) Lentiviral transduction No Human BL, DLBCL Preclinical 2020 [86]
CB irradiated k562-mbIL21-41BBL Yes (anti-CD19 CAR-IL15-iC9) Retroviral transdduction No Human BL Preclinical 2019 [56]
PB IL12, IL15, IL18 Yes (anti-CD19 CAR) N/A No Human BL Preclinical 2020 [91]
iPSC (FT596) N/A Yes (anti-CD19 CAR-hnCD16-IL15RF) N/A rituximab Human BL Preclinical 2019 [92]
PB irradiated k562-mbIL15-41BBL No No Obinutuzumab Human BL Preclinical 2015 [93]
PB No No No CD19/CD16 BiKE CD19/CD22/CD16 TriKE Human BL Preclinical 2012 [94•]
PB No No No 161519 TriKE Human BL Preclinical 2012 [95]
PB No No No CD30/CD16A (AFM13) tandem diabody Human HL Preclinical 2014 [96]
PB No No No rituximab Human BL FL Preclinical 2016 [97]
PB No No No N-820 Human BL Preclinical 2016 [98]
PB irradiated k562-mbIL21-41BBL No No N-820 rituximab sensitive and resistant human BL Preclinical 2020 [99]

CB cord blood; PB peripheral blood; hESC human embryonic stem cell; SCF stem cell factor; Flt3L Flt3 ligand; iPSC induced pluripotent stem cell; ML memory-like; NAM nicotinamide; iC9 inducible caspase-9; CAR chimeric antigen receptor; hnCD16 high-affinity, non-cleavable CD16; BL Burkitt lymphoma; FL follicular lymphoma; mRNA messenger ribonucleic acid; Ref. references