A novel endogenous CD16-Expressing Natural Killer Cell for cancer immunotherapy

Cheng, Zih-Fei; Li, Hao-Kang; Yang, Hsiu-Ping; Lee, Chia‐Yun; Tang, Sai-Wen; Lin, Yen‐Ting; Hsiao, Shih-Chia

doi:10.1016/j.bbrep.2021.100935

Cited by 12 publications

(10 citation statements)

References 44 publications

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“…To capacitate oNK cells with HER-targeting specificity, ACC technology was applied to conjugate trastuzumab on oNK cells (ACE-oNK-HER2), which provided >10 fold more antibodies on cell surfaces than those by Fc domain binding (oNK + trastuzumab, Figure 1 B). CD56 and CD16 have been shown to characterize oNK [ 27 ]. The populations of CD56 + CD3 - and CD16 + cells were not influenced by trastuzumab conjugation ( Figure 1 C).…”

Section: Resultsmentioning

confidence: 99%

“…Patients harboring CD16 with a high affinity to antibodies (i.e., CD16 158 v/v genotype) exhibited a good overall response rate [ 51 ]. In this study, oNK cells harboring CD16 genotype with high affinity to antibody [ 27 ] were covalently conjugated with trastuzumab through paired ssDNA linkers ( Figure 1 B). Our results revealed that cytotoxicity of ACE-oNK-HER2 against SK-OV-3, SK-BR-3 and MCF-7 cells was remarkably enhanced at an E:T ratio as low as 1:1 compared to Ctrl-oNK ( Figure 2 A–C).…”

Section: Discussionmentioning

confidence: 99%

“…These cell lines were cultured according to ATCC guidelines. oNK cells were cultured as described previously [ 27 ]. Female peripheral blood mononuclear cells (PBMC) were bought from PPA Research Group and cultured under the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…In a recent study, we established a novel endogenous CD16-expressing oNK cell line (oNK) with antibody-dependent cellular cytotoxicity (ADCC), as well as a preferential expression of NK activation receptors and low level of inhibitory receptors [ 27 ]. Here, we applied the ACC platform to conjugate trastuzumab on oNK cells and demonstrated its superior in vitro and in vivo potency against HER2-expressing cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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A Novel off-the-Shelf Trastuzumab-Armed NK Cell Therapy (ACE1702) Using Antibody-Cell-Conjugation Technology

Hsiao

Yang

et al. 2021

Cancers

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Natural killer (NK) cells harbor efficient cytotoxicity against tumor cells without causing life-threatening cytokine release syndrome (CRS) or graft-versus-host disease (GvHD). When compared to chimeric antigen receptor (CAR) technology, Antibody-Cell Conjugation (ACC) technology has been developed to provide an efficient platform to arm immune cells with cancer-targeting antibodies to recognize and attack cancer cells. Recently, we established an endogenous CD16-expressing oNK cell line (oNK) with a favorable expression pattern of NK activation/inhibitory receptors. In this study, we applied ACC platform to conjugate oNK with trastuzumab and an anti-human epidermal growth factor receptor 2 (HER2) antibody. Trastuzumab-conjugated oNK, ACE-oNK-HER2, executed in vitro and in vivo cytotoxicity against HER2-expressing cancer cells and showed enhanced T cell-recruiting capability and secretion of IFNγ. The irradiated and cryopreserved ACE-oNK-HER2, designated as ACE1702, retained superior HER2-specific in vitro and in vivo potency with no tumorigenic potential. In conclusion, this study provides the evidence to support the potential clinical application of ACE1702 as a novel off-the-shelf NK cell therapy against HER2-expressing solid tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Novel off-the-Shelf Trastuzumab-Armed NK Cell Therapy (ACE1702) Using Antibody-Cell-Conjugation Technology

Hsiao

Yang

et al. 2021

Cancers

Self Cite

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“…Indeed, it has been recently shown that an adapted subpopulation of NK-92 expressing functional endogenous CD16 and further modified with the conjugation with Trastuzumab, an anti-human epidermal growth factor receptor 2 (HER-2) antibody, displayed enhanced cytotoxicity against HER-2-positive targets in vivo and in vitro. The absence of cell manipulation with viral vector or transposon systems, possibly mediating viral insertion mutation and imprecise chromosomal insertion, respectively, could represent an advantage with respect to other engineered products [ 145 , 146 ].…”

Section: Adoptive Transfer Of Nk Cellsmentioning

confidence: 99%

NK Cell-Based Immunotherapy in Colorectal Cancer

et al. 2022

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Human Natural Killer (NK) cells are all round players in immunity thanks to their powerful and immediate response against transformed cells and the ability to modulate the subsequent adaptive immune response. The potential of immunotherapies based on NK cell involvement has been initially revealed in the hematological setting but has inspired the design of different immune tools to also be applied against solid tumors, including colorectal cancer (CRC). Indeed, despite cancer prevention screening plans, surgery, and chemotherapy strategies, CRC is one of the most widespread cancers and with the highest mortality rate. Therefore, further efficient and complementary immune-based therapies are in urgent need. In this review, we gathered the most recent advances in NK cell-based immunotherapies aimed at fighting CRC, in particular, the use of monoclonal antibodies targeting tumor-associated antigens (TAAs), immune checkpoint blockade, and adoptive NK cell therapy, including NK cells modified with chimeric antigen receptor (CAR-NK).

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