Clinical-grade generation of active NK cells from cord blood hematopoietic progenitor cells for immunotherapy using a closed-system culture process.
Jan Spanholtz,Frank Preijers,Marleen Tordoir,Carel Trilsbeek,Jos Paardekooper,Theo de Witte,Nicolaas Schaap,Harry Dolstra +7 more
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It is demonstrated that large numbers of UCB stem cell-derived NK cell products for adoptive immunotherapy can be produced in closed, large-scale bioreactors for the use in clinical trials.Abstract:
Natural killer (NK) cell-based adoptive immunotherapy is a promising treatment approach for many cancers. However, development of protocols that provide large numbers of functional NK cells produced under GMP conditions are required to facilitate clinical studies. In this study, we translated our cytokine-based culture protocol for ex vivo expansion of NK cells from umbilical cord blood (UCB) hematopoietic stem cells into a fully closed, large-scale, cell culture bioprocess. We optimized enrichment of CD34+ cells from cryopreserved UCB units using the CliniMACS system followed by efficient expansion for 14 days in gas-permeable cell culture bags. Thereafter, expanded CD34+ UCB cells could be reproducibly amplified and differentiated into CD56+CD3− NK cell products using bioreactors with a mean expansion of more than 2,000 fold and a purity of >90%. Moreover, expansion in the bioreactor yielded a clinically relevant dose of NK cells (mean: 2×109 NK cells), which display high expression of activating NK receptors and cytolytic activity against K562. Finally, we established a versatile closed washing procedure resulting in optimal reduction of medium, serum and cytokines used in the cell culture process without changes in phenotype and cytotoxic activity. These results demonstrate that large numbers of UCB stem cell-derived NK cell products for adoptive immunotherapy can be produced in closed, large-scale bioreactors for the use in clinical trials.read more
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NK cells for cancer immunotherapy.
TL;DR: New approaches to activate NK cells, increase their proliferation in vivo and increase their capacity to recognize tumour cells are discussed.
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NK cell-based immunotherapy for malignant diseases
TL;DR: Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells are discussed, and a list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here.
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Exploring the NK cell platform for cancer immunotherapy
Jacob A. Myers,Jeffrey S. Miller +1 more
TL;DR: The authors discuss the variety of NK cell-based therapies that are being developed for the treatment of diverse cancers and identify future avenues for NK cell therapy research.
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CAR-NK cells: A promising cellular immunotherapy for cancer
TL;DR: Current challenges and future promise of CAR-NK cells as a novel cellular immunotherapy in cancer are discussed, and they could be engineered to target diverse antigens, enhance proliferation and persistence in vivo, increase infiltration into solid tumours, overcome resistant tumour microenvironment, and ultimately achieve an effective anti-tumour response.
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NK cell-based immunotherapy for cancer.
TL;DR: The current progress on NK cell-based therapeutic approaches, NK cell manufacturing techniques and tumor therapy outcomes are discussed.
References
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An international system for human cytogenetic nomenclature
TL;DR: An exceptional reading e-book entitled International System For Human Cytogenetic Nomenclature provides a thorough legal analysis and guidance to state authorities, human rights and humanitarian actors and others.
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Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants
Loredana Ruggeri,Marusca Capanni,Elena Urbani,Katia Perruccio,Warren D. Shlomchik,Antonella Tosti,Sabrina Posati,Daniela Rogaia,Francesco Frassoni,Franco Aversa,Massimo F. Martelli,Andrea Velardi +11 more
TL;DR: It is shown that donor-versus-recipient natural killer (NK)–cell alloreactivity could eliminate leukemia relapse and graft rejection and protect patients against GVHD in human transplants and in mice, the pretransplant infusion of alloreactive NK cells obviated the need for high-intensity conditioning and reduced GV HD.
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Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.
Jeffrey S. Miller,Yvette Soignier,Angela Panoskaltsis-Mortari,Sarah A. McNearney,Gong H. Yun,Susan K. Fautsch,David H. McKenna,Chap T. Le,Todd E. DeFor,Linda J. Burns,Paul J. Orchard,Bruce R. Blazar,John E. Wagner,Arne Slungaard,Daniel J. Weisdorf,Ian J. Okazaki,Philip B. McGlave +16 more
TL;DR: It is suggested that haploidentical NK cells can persist and expand in vivo and may have a role in the treatment of selected malignancies used alone or as an adjunct to HCT.
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CD107a as a functional marker for the identification of natural killer cell activity
TL;DR: It is suggested that employing CD107a as a marker of NK cell functional activity may allow for the identification of a large fraction of activated NK cells that may degranulate in the absence of cytokine secretion.
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Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution.
Pablo Rubinstein,Ludy Dobrila,Richard E. Rosenfield,John W. Adamson,Giovanni Migliaccio,Anna Rita Migliaccio,Patricia E. Taylor,Cladd E. Stevens +7 more
TL;DR: Almost all the hematopoietic colony-forming cells present in PCB units can be recovered in a uniform volume of 20 ml by using rouleaux formation induced by hydroxyethyl starch and centrifugation to reduce the bulk of erythrocytes and plasma and, thus, concentrate leukocytes.