Abstract
Natural killer cells (NK cells) are the first line of the innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected and malignant cells through a balancing play of inhibitory and stimulatory receptors. In pre-clinical investigational studies, NK cells show promising anti-tumor effects and are used in adoptive transfer of activated and expanded cells, ex-vivo. NK cells express co-stimulatory molecules that are attractive targets for the immunotherapy of cancers. Recent clinical trials are investigating the use of CAR-NK for different cancers to determine the efficiency. Herein, we review NK cell therapy approaches (NK cell preparation from tissue sources, ways of expansion ex-vivo for “off-the-shelf” allogeneic cell-doses for therapies, and how different vector delivery systems are used to engineer NK cells with CARs) for cancer immunotherapy.
Highlights
Natural Killer (NK) cells are critical in immune surveillance of invading viruses and kill tumor cells without the need of tumor specific antigen presentation
Pre-clinical data from early phase clinical trials has significantly increased our knowledge for the use of allogeneic donor NK cells across a wide range of hematological malignancies and solid tumors
Matching, genetic modification to create chimeric antigen receptor (CAR)-NK constructs, and transfer of genetic material using viral and nonviral delivery technologies. These advances point towards a true “off-the-shelf” NK cell therapy
Summary
Study Start: April 2013 Primary Completion: March 15, 2018 Last Update Posted: July 12, 2018 Study Start: January 29, 2011 Primary Completion: June 28, 2018 Last Update Posted: August 22, 2019 Study Start: March 28, 2016 Primary Completion: June 2, 2017 Last Update Posted: July 31, 2017 Study Start: April 2, 2009 Primary Completion: January 7, 2019 Last Update Posted: January 10, 2019. National Institutes of Health Clinical Center, Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. NCT02301065 Analysis of T Cell and Natural Killer (NK) Cell in Relation to Viral Infections in Pediatric Stem Cell Transplant Patients and Donors. Blood derived FcRg-CD56 +CD3- NK cells in pediatric allogeneic HSCT patients and healthy donors. NCT02845999 Allogenic Immunotherapy Based on Natural Killer (NK) Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab
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