Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21

Thangaraj, Jaya Lakshmi; Phan, Minh‐Trang Thi; Kweon, SoonHo; Kim, Jin-Ho; Lee, Jongmin; Hwang, Ilwoong; Park, Jeehun; Doh, Junsang; Lee, Seung Hwan; Vo, Manh-Cuong; Chu, Tan-Huy; Song, Ga‐Young; Ahn, Seo-Yeon; Jung, Sung-Hoon; Kim, Hyeoung-Joon; Cho, Duck; Lee, Je‐Jung

doi:10.1007/s00262-021-02982-9

Cited by 18 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other authors actively tried to further optimize the NK cell expansion protocols. Thus, Thangaraj et al [ 53 ] cultured PBMC with a K562–OX40L–membrane IL-18–membrane IL-21 feeder cell line in the presence of soluble IL-2/IL-15, and observed a 9.860 fold increase in NK cell numbers from healthy donors versus 4.929 fold from multiple myeloma patients, in which NK cells are usually dysfunctional, after a culture period of four weeks [ 53 ]. These NK cells (over 80% purity) were highly cytotoxic to the three tested tumor cell lines and upregulated the most important AR [ 53 ].…”

Section: Methods For the Massive Expansion Of Nk Cells For Immunotherapymentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

View full text Add to dashboard Cite

Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

show abstract

Section: Methods For the Massive Expansion Of Nk Cells For Immunotherapymentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…In an interesting study, Li et al demonstrated while increasing concentration of IL-21 (1-10 ng/ml) resulted in higher cytotoxicity through upregulation of IFN-g and granzyme B, at high concentrations (50 ng/ml) IL-21 resulted in NK cell apoptosis (101). Notably, several groups now routinely utilize irradiated NK cell-sensitive tumor cells that express membrane-bound IL-21 (mbIL-21) and other stimulatory ligands (e.g., 4-1BBL or Ox40L) to stimulate prolonged and large-scale expansion of NK cells (29,31,(102)(103)(104).…”

Section: Effects Of Other Cytokines and Chemokines On Nk Cell Expansi...mentioning

confidence: 99%

iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting

2022

View full text Add to dashboard Cite

Treatment of cancer with allogeneic natural killer (NK) cell therapies has seen rapid development, especially use against hematologic malignancies. Clinical trials of NK cell-based adoptive transfer to treat relapsed or refractory malignancies have used peripheral blood, umbilical cord blood and pluripotent stem cell-derived NK cells, with each approach undergoing continued clinical development. Improving the potency of these therapies relies on genetic modifications to improve tumor targeting and to enhance expansion and persistence of the NK cells. Induced pluripotent stem cell (iPSC)-derived NK cells allow for routine targeted introduction of genetic modifications and expansion of the resulting NK cells derived from a clonal starting cell population. In this review, we discuss and summarize recent important advances in the development of new iPSC-derived NK cell therapies, with a focus on improved targeting of cancer. We then discuss improvements in methods to expand iPSC-derived NK cells and how persistence of iPSC-NK cells can be enhanced. Finally, we describe how these advances may combine in future NK cell-based therapy products for the treatment of both hematologic malignancies and solid tumors.

show abstract

“…All CRC cell lines were cultured in Roswell Park Memorial Institute (RPMI)-1640 medium (Gibco, USA) supplemented with 10% fetal bovine serum (FBS; HyClone, USA) and 1% penicillin-streptomycin (PS; Gibco, USA). Primary NK cells were expanded from peripheral blood mononuclear cells (PBMCs) by co-culturing with 100 Gyirradiated K562-OX40L-membrane-bound (mb) IL-18/21 feeder cells (23). In particular, human PBMCs were isolated from healthy adult donors using density-gradient centrifugation with Ficoll-Hypaque (d = 1.077, LymphoprepTM; Axis-Shield, Oslo, Norway) and washed twice with phosphate-buffered saline (PBS) (Welgene, USA).…”

Section: Cell Culturementioning

confidence: 99%

“…We compared the cytotoxicity of primary NK cells on a conventional 2D cell culture dish to our 3D culture platform. Primary NK cells used in our assays were expanded from PBMCs using genetically engineered feeder cells developed in previous research (23). After NK cells were added to the 2D cell culture dish, most cancer cells were dead within 4 h (Supplementary Figure S3A), while NK cells in our 3D tumor vasculature model had relatively slower cytotoxic effects, which involved additional processes including NK cell extravasation and intravasation (Supplementary Figures S3B-D).…”

Section: Validation Of Nk Cell Infiltration and Cytotoxicity In The Complex 3d Tmementioning

confidence: 99%

High-Throughput 3D In Vitro Tumor Vasculature Model for Real-Time Monitoring of Immune Cell Infiltration and Cytotoxicity

et al. 2021

Self Cite

View full text Add to dashboard Cite

Recent advances in anticancer therapy have shown dramatic improvements in clinical outcomes, and adoptive cell therapy has emerged as a type of immunotherapy that can modulate immune responses by transferring engineered immune cells. However, a small percentage of responders and their toxicity remain as challenges. Three-dimensional (3D) in vitro models of the tumor microenvironment (TME) have the potential to provide a platform for assessing and predicting responses to therapy. This paper describes an in vitro 3D tumor model that incorporates clusters of colorectal cancer (CRC) cells around perfusable vascular networks to validate immune-cell-mediated cytotoxicity against cancer cells. The platform is based on an injection-molded 3D co-culture model and composed of 28 microwells where separate identical vascularized cancer models can be formed. It allows robust hydrogel patterning for 3D culture that enables high-throughput experimentation. The uniformity of the devices resulted in reproducible experiments that allowed 10× more experiments to be performed when compared to conventional polydimethylsiloxane (PDMS)-based microfluidic devices. To demonstrate its capability, primary natural killer (NK) cells were introduced into the vascularized tumor network, and their activities were monitored using live-cell imaging. Extravasation, migration, and cytotoxic activity against six types of CRC cell lines were tested and compared. The consensus molecular subtypes (CMS) of CRC with distinct immune responses resulted in the highest NK cell cytotoxicity against CMS1 cancer cells. These results show the potential of our vascularized tumor model for understanding various steps involved in the immune response for the assessment of adoptive cell therapy.

show abstract

Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21

Cited by 18 publications

References 35 publications

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting

High-Throughput 3D In Vitro Tumor Vasculature Model for Real-Time Monitoring of Immune Cell Infiltration and Cytotoxicity

Contact Info

Product

Resources

About