A5030981061- CAR-T cell therapy research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Hematopoietic Stem Cell Transplantation
- Lymphoma Diagnosis and Treatment
Nationwide Children's Hospital
2020-2023
The Ohio State University
2023
Human primary natural killer (NK) cells are being widely advanced for cancer immunotherapy. However, methods gene editing of these have suffered low transduction rates, high cell death, and loss transgene expression after expansion. Here, we developed a highly efficient method site-specific insertion in NK using CRISPR (Cas9/RNP) AAVs. We compared AAV vectors designed to mediate by different DNA repair mechanisms, homology arm lengths, virus concentrations. then validated the site-directed...
Abstract Background Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin subtype which remains incurable despite multimodal approach including chemoimmunotherapy followed by stem transplant, targeted approaches such as the BTK inhibitor ibrutinib, and CD19 chimeric antigen receptor (CAR) T cells. CD74 nonpolymorphic type II integral membrane glycoprotein identified an MHC class chaperone for macrophage migration inhibitory factor. Our group previously reported on CD74's abundant...
Abstract Human peripheral blood natural killer (NK) cells have intense antitumor activity and been used successfully in several clinical trials. Modifying NK with a chimeric antigen receptor (CAR) can improve their targeting increase specificity. Recently, we described an efficient method for gene using Cas9/ribonucleoprotein (RNP) complexes. Here combined this approach single-stranded (ss) or self-complementary (sc) Adeno-associated virus (AAV)-mediated delivery insertion into safe-harbor...
Human peripheral blood natural killer (NK) cells have intense antitumor activity and been used successfully in several clinical trials. Modifying NK with a chimeric antigen receptor (CAR) can improve their targeting increase specificity, but genetic modification of primary human has problematic compared to the ease which T are transduced. Despite some progress made using lentiviral retroviral vectors, efficiency viral transduction remains relatively low. Additionally, these vectors results...
Loss of cytotoxicity and defective metabolism are linked to glycogen synthase kinase 3 beta (GSK3β) overexpression in natural killer (NK) cells from patients with acute myeloid leukemia or healthy donors after expansion ex vivo IL-15. Drug inhibition GSK3β these NK improves their maturation cytotoxic activity, but the mechanisms GSK3β-mediated dysfunction have not been well studied. Here, we show that feeder expressing membrane-bound IL-21 maintained normal levels, allowing us study function...