Clinical-Scale Derivation of Natural Killer Cells From Human Pluripotent Stem Cells for Cancer Therapy

Knorr, David A.; Ni, Zhenya; Hermanson, David; Hexum, Melinda K.; Bendzick, Laura; Cooper, Laurence J.N.; Lee, Dean A.; Kaufman, Dan S.

doi:10.5966/sctm.2012-0084

Cited by 323 publications

(361 citation statements)

References 29 publications

Supporting

Mentioning

340

Contrasting

Unclassified

Order By: Relevance

“…First, each line provides an unlimited number of cells and serves as an individual donor allowing a homogenous starting source. Our most recent studies have improved on the method in generating NK cells from hESCs and iPSCs, allowing the generation of enough cells to treat a single patient from 250,000 starting cells [17]. Second, hESCs and iPSCs are genetically amenable platforms allowing stable transgene expression.…”

Section: Discussionmentioning

confidence: 99%

Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

Knorr

Bock

Brentjens

et al. 2013

Stem Cells and Development

Self Cite

View full text Add to dashboard Cite

Human embryonic stem cell (hESC)-derived natural killer (NK) cells are a promising source of antitumor lymphocytes for immunotherapeutics. They also provide a genetically tractable platform well suited for the study of antitumor immunotherapies in preclinical models. We have previously demonstrated the potency of hESC-derived NK cells in vivo. Here we use both bioluminescent and fluorescent imaging to demonstrate trafficking of hESC-derived NK cells to tumors in vivo. Our dual-imaging approach allowed us to more specifically define the kinetics of NK cell trafficking to tumor sites. NK cell persistence and trafficking were further evaluated by flow cytometry and immunohistochemistry. This integrated approach provides a unique system to apply the use of human pluripotent stem cells to study the kinetics and biodistribution of adoptively transferred lymphocytes, advances broadly applicable to the field of immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

Knorr

Bock

Brentjens

et al. 2013

Stem Cells and Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…As another feeder-free culture method, Spanholtz and colleagues reported a culture method that achieved amplification efficiency and high purity of 10,000 times or more in 6 weeks from UCB CD34 + hematopoietic stem cell (HSCs), using a closed system process based on GMP [85]. Knorr and colleagues reported differentiation induction from CD34 + hematopoietic progenitor cells produced under feeder-free conditions to cytotoxic NK cells [86].…”

Section: Manufacturing Methodsmentioning

confidence: 99%

Clinical Applications of Natural Killer Cells

Harada¹,

Teraishi²,

Ishii³

et al. 2017

Natural Killer Cells

View full text Add to dashboard Cite

Natural killer (NK) cells are an essential component of the innate immune system, and they play a crucial role in immunity against malignancies. Recent advances in our understanding of NK cell biology have paved the way for new therapeutic strategies based on NK cells for the treatment of various cancers. In this section, we will focus on NK cell immunotherapy, including the enhancement of antibody-dependent cellular cytotoxicity, the manipulation of receptor-mediated activation, inclusion criteria based on killer cell immunoglobulin-like receptor (KIR) ligand mismatches, and adoptive immunotherapy with ex vivo expanded chimeric antigen receptor (CAR)-engineered or engager-modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack any recipient tissues based on allogeneic human leukocyte antigens (HLAs), suggesting that NK-mediated antitumor effects may be achieved without the risk of graft-versus-host disease (GvHD). Despite reports of clinical efficacy, the application of NK cell immunotherapy is limited. Developing strategies for manipulating NK cell products, host factors, and tumor targets are thus current subjects of diligent study. Research into the biology of NK cells has indicated that NK cell immunotherapy has the potential to become the forefront of cancer immunotherapy in the coming years.

show abstract

“…Subsequently, using the similar culture system, NK cells were also successfully differentiated from human iPS cells. Importantly, these iPSCs-derived NK cells had the potential to actively suppress human tumor cells and they produced high levels of interferon-γ [40]. In a recent study, it has been shown that NKT cells could also be derived from iPS cells.…”

Section: Ipscs In Cancer Immunotherapymentioning

confidence: 99%

Current challenges in the therapeutic use of induced pluripotent stem cells (iPSCs) in cancer therapy

Potdar

Chaudhary

2017

Appl Cancer Res

View full text Add to dashboard Cite

Induced Pluripotent Stem Cells (iPSCs) technology has catapulted the field of stem-cell biology through ectopic expression of reprogramming factors. Ever since its discovery, the potential of iPSCs has been explored by many scientists to unravel the molecular mechanism responsible for cancer initiation and progression. Besides modeling cancer, the further applications of this technology includes high-throughput drug screening, epigenetic reprogramming of cancer cell state to normal, immunotherapy and regenerative cell therapies. Here, we review the current challenges on clinical applications of iPSCs with respect to understanding cancer and personalizing treatment for the disease.

show abstract

Clinical-Scale Derivation of Natural Killer Cells From Human Pluripotent Stem Cells for Cancer Therapy

Abstract: MEDICINE 2013;2:274 -283

Cited by 323 publications

References 29 publications

Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

Clinical Applications of Natural Killer Cells

Current challenges in the therapeutic use of induced pluripotent stem cells (iPSCs) in cancer therapy

Contact Info

Product

Resources

About