Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model

Thangaraj, Jaya Lakshmi; Ahn, Seo-Yeon; Jung, Sung‐Hoon; Vo, Manh-Cuong; Chu, Tan-Huy; Phan, Minh‐Trang Thi; Kwon, Minsuk; Lee, Kyung‐Hwa; Kim, Mi-Hee; Song, Ga‐Young; Yang, Deok‐Hwan; Ahn, Jae‐Sook; Kim, Hyeoung-Joon; Cho, Duck; Lee, Je‐Jung

doi:10.1038/s41423-021-00686-9

Cited by 21 publications

(25 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there is no evidence reported previously regarding how many T cells would be required to induce GVHD, even in mouse model. It has been reported that infusion of 2 × 10 7 NK cells/dose/mouse, in which less than 5% of T cells were present, was safe, and no GVHD was observed in mouse models [ 14 , 47 ]. Whereas, our data observed in Figure 7 demonstrated that although our dose was 1.6 × 10 7 CD56 + cells/dose/mouse (equal to 2 × 10 7 cells/mouse × 3 doses), which contained up to 1.2 × 10 7 T cells/mouse, it would not induce GvHD.…”

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Chen

et al. 2021

Cancers

View full text Add to dashboard Cite

Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 107 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Chen

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Among various approaches, adoptive NK therapy, which involves ex vivo expanded and activated NK cells has emerged as a promising solution to overcome immunosuppression commonly observed in solid tumors by increasing the number and antitumor activity of NK cells ( 39 ). Therefore, we used NK cells that were expanded and activated according to the previously established protocol by using a feeder cell, K562 expressing the OX40 ligand and membrane-bound IL-18 and IL-21, which showed potential effects on multiple myeloma in the previous study ( 23 ); we wanted to confirm the therapeutic effects of these established NK cells in the GBM setting. Interestingly, NK-GBM showed no difference compared to NK-HDs in terms of purity, expansion fold, activated markers, and slightly lower cytotoxic effects against GBM cells with this established protocol.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the combination of NK cells with other treatment methods in current preclinical efforts enhances the efficacy of NK cell-based therapy. Furthermore, NK cells expanded and activated by K562-OX40L-mb-IL-18/IL-21 feeder cells have shown cytotoxic activity against multiple myeloma in in vitro and xenograft mouse models ( 23 – 25 ). Therefore, NK cells using K562-OX40L-mb-IL-18/IL-21 cells as feeder cells were also used to confirm therapeutic effects against GBM in this study.…”

Section: Introductionmentioning

confidence: 99%

Natural killer cell therapy potentially enhances the antitumor effects of bevacizumab plus irinotecan in a glioblastoma mouse model

et al. 2023

Self Cite

View full text Add to dashboard Cite

Various combination treatments have been considered to attain the effective therapy threshold by combining independent antitumor mechanisms against the heterogeneous characteristics of tumor cells in malignant brain tumors. In this study, the natural killer (NK) cells associated with bevacizumab (Bev) plus irinotecan (Iri) against glioblastoma multiforme (GBM) were investigated. For the experimental design, NK cells were expanded and activated by K562 cells expressing the OX40 ligand and membrane-bound IL-18 and IL-21. The effects of Bev and Iri on the proliferation and NK ligand expression of GBM cells were evaluated through MTT assay and flow cytometry. The cytotoxic effects of NK cells against Bev plus Iri-treated GBM cells were also predicted via the LDH assay in vitro. The therapeutic effect of different injected NK cell routes and numbers combined with the different doses of Bev and Iri was confirmed according to tumor size and survival in the subcutaneous (s.c) and intracranial (i.c) U87 xenograft NOD/SCID IL-12Rγnull mouse model. The presence of injected-NK cells in tumors was detected using flow cytometry and immunohistochemistry ex vivo. As a result, Iri was found to affect the proliferation and NK ligand expression of GBM cells, while Bev did not cause differences in these cellular processes. However, the administration of Bev modulated Iri efficacy in the i.c U87 mouse model. NK cells significantly enhanced the cytotoxic effects against Bev plus Iri-treated GBM cells in vitro. Although the intravenous (IV) injection of NK cells in combination with Bev plus Iri significantly reduced the tumor volume in the s.c U87 mouse model, only the direct intratumorally (IT) injection of NK cells in combination with Bev plus Iri elicited delayed tumor growth in the i.c U87 mouse model. Tumor-infiltrating NK cells were detected after IV injection of NK cells in both s.c and i.c U87 mouse models. In conclusion, the potential therapeutic effect of NK cells combined with Bev plus Iri against GBM cells was limited in this study. Accordingly, further research is required to improve the accessibility and strength of NK cell function in this combination treatment.

show abstract

“…Adoptive transfer of NK cells exploits the effector functions of ex vivo expanded NK cells ( 83 ), from NK cell line, cord blood, peripheral blood, or induced pluripotent stem cells (iPSCs). Such strategy has shown safety ( 84 , 85 ) and therapeutic potential for the control of various viruses, not only in mouse models, but also in clinical trials.…”

Section: Nk Cell Therapymentioning

confidence: 99%

Prospects for NK-based immunotherapy of chronic HBV infection

Jin

2022

Front. Immunol.

View full text Add to dashboard Cite

Effective and long-term treatment is required for controlling chronic Hepatitis B Virus (HBV) infection. Natural killer (NK) cells are antiviral innate lymphocytes and represent an essential arm of current immunotherapy. In chronic HBV (CHB), NK cells display altered changes in phenotypes and functions, but preserve antiviral activity, especially for cytolytic activity. On the other hand, NK cells might also cause liver injury in the disease. NK -based immunotherapy, including adoptive NK cell therapy and NK -based checkpoint inhibition, could potentially exploit the antiviral aspect of NK cells for controlling CHB infection while preventing liver tissue damage. Here, we review recent progress in NK cell biology under the context of CHB infection, and discuss potential NK -based immunotherapy strategies for the disease.

show abstract

Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model

Cited by 21 publications

References 48 publications

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Natural killer cell therapy potentially enhances the antitumor effects of bevacizumab plus irinotecan in a glioblastoma mouse model

Prospects for NK-based immunotherapy of chronic HBV infection

Contact Info

Product

Resources

About