Natural Killer (NK) and CAR-NK Cell Expansion Method using Membrane Bound-IL-21-Modified B Cell Line.

J Vis Exp

Department of Pathology, Immunology and Laboratory Medicine, Rutgers-New Jersey Medical School; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey;

Published: February 2022

Similar Publications

Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells. These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups.

View Article and Find Full Text PDF

Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells.

Mol Ther

January 2025

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin, 53715, USA; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, 53715, USA. Electronic address:

Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood.

View Article and Find Full Text PDF

Uncovering mechanisms and predicting tumor cell responses to CAR-NK cytotoxicity is essential for improving therapeutic efficacy. Currently, the complexity of these effector-target interactions and the donor-to-donor variations in NK cell receptor (NKR) repertoire require functional assays to be performed experimentally for each manufactured CAR-NK cell product and target combination. Here, we developed a computational mechanistic multiscale model which considers heterogenous expression of CARs, NKRs, adhesion receptors and their cognate ligands, signal transduction, and NK cell-target cell population kinetics.

View Article and Find Full Text PDF

iPSC-derived CD19 CAR NK cells for relapsed or refractory lymphoma.

Lancet

January 2025

Division of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address:

View Article and Find Full Text PDF

CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Cell Rep Med

December 2024

Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 311121, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou 310058, China. Electronic address:

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!