Table 3.
Efficacy of engineered NK cells in enhancing FDA approved mAbs-mediated ADCC.
| Engineered NK cells | Combination | Study | Efficacy | Reference |
|---|---|---|---|---|
| Immunoligands | Immunoligands fusing the extracellular domains of ligands of the activating NK cell receptors to a scFv targeting HER2 on different solid tumors | Preclinical | Enhanced ADCC mediated by trastuzumab and cetuximab against HER2 positive cancer cells | (171, 172) |
| Rituximab with CD20-specific immunoligands targeting NKG2D | Preclinical | Enhanced ADCC mediated by rituximab against B-chronic lymphocytic leukaemia and Burkitt's lymphoma cell lines | (173) | |
| Expanded ex vivo NK cells | Expanded NK cells in combination with trastuzumab and cetuximab | Phase I in patients with gastric or colorectal cancer | Four patients achieved SD. Reduction of tumor size in three patients with SD | (174) |
| Trastuzumab in combination with autologous NK cells expanded with K562-mb15-41BBL cells | Phase I in patients with treatment-refractory HER2-positive solid tumors | Six patients achieved SD for ≥6 months | (175) | |
| Expanded autologous NK cells with IL-15 in combination with rituximab | Phase I in patients with relapsed CD20-positive malignant lymphoma | NK cells enhanced ADCC mediated by rituximab. Seven patients maintained CR with a median duration of 44 months | (176) | |
| Expanded allogeneic NK cells in combination with rituximab | Phase I in patients with relapsed/refractory B cell non-Hodgkin lymphoma |
PR in 4 patients and CR in 1 patient, with an overall response rate of 55.6% | (177) | |
| NK cells stimulated with nicotamide in combination with rituximab | Phase I in patients with advanced non-Hodgkin lymphoma | ORR of 74% in 19 patients, CR in 13 patients, PR in 1 patient | (178) | |
| Expanded NK cells in combination with cetuximab | Phase I/II in patients with NSCLC | Longer PFS, reduction of levels of circulating cancer cells compared to patients treated with cetuximab alone | (179) | |
| Autologous NK cells, expanded by co-culture with irradiated K562-mb15-41BBL cells in combination with cetuximab | Phase I in patients with recurrent/metastatic nasopharyngeal carcinoma | SD in 4 out of 7 patients | (180) | |
| Immortalized NK cell lines | haNK cell line in combination with trastuzumab, cetuximab and avelumab | Preclinical | haNK potentiated in vitro ADCC activity of mAbs | (181–183) |
| NK92-41BB cell line harboring CD16/CAR with high affinity for Fc portion of mAbs in combination with trastuzumab and rituximab | Preclinical | Enhanced ADCC activity | (184) | |
| Endogenous CD16-expressing NK cell line (oNK) conjugated with trastuzumab |
Preclinical | Enhanced cytotoxicity against cancer cells expressing HER2 | (185) |