Immunotherapy, particularly CAR-T therapy has recently emerged as an innovator for cancer treatment. Gamma-irradiated K562 cells is a common and effective method to stimulated CAR-T cells prior to treatment. However, high cost and limited equipment of gamma-irradiation is drawback of this method. This requires the establishment of CAR-T-expanding alternatives, such as X-ray-irradiated K562 cells. X-ray irradiation was used to deactivate K562 cells. The post-irradiative cell survival was investigated by counting of the number of cells, staining with Trypan Blue and PI. FACS analysis was applied to detect the expression of cell surface markers. The production of CD19-CAR-T cells were executed from fresh blood donor by CD19-CAR-plasmid transfection, followed by the stimulation with X-ray-irradiated K562 feeder cells. The function of produced CAR-T cells was checked by their ability to kill Daudi cells. X-ray-irradiation inhibited the propagation and viability of K562 cells in a dose- and time-dependent manner. Interestingly, CAR-T-stimulating effectors were remained on the surface of X-ray-irradiated K562 cells. CD-19-CAR-T cells were produced successfully, suggested by number of CAR-positive cells in transfected and stimulated population, compared to un-transfected group. Lastly, our data showed that engineered CAR-T cells effectively killed Daudi cells. Our data demonstrated the efficacy of X-ray on deactivation K562 feeder cells which subsequently stimulated and expanded functional CAR-T cells. Thus, X-ray can be used as an alternative to inactivate K562 cells prior to using as a feeder of CAR-T cells.
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http://dx.doi.org/10.1016/j.bbrep.2022.101399 | DOI Listing |
Cell Prolif
December 2024
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The recent advancements in cancer immunotherapy have spotlighted the potential of natural killer (NK) cells, particularly chimeric antigen receptor (CAR)-transduced NK cells. These cells, pivotal in innate immunity, offer a rapid and potent response against cancer cells and pathogens without the need for prior sensitization or recognition of peptide antigens. Although NK cell genetic modification is evolving, the viral transduction method continues to be inefficient and fraught with risks, often resulting in cytotoxic outcomes and the possibility of insertional mutagenesis.
View Article and Find Full Text PDFCancer Cell
December 2024
Genome Institute of Singapore, Agency for Science, Technology, and Research (A(∗)STAR), 60 Biopolis Street, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore. Electronic address:
Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.
View Article and Find Full Text PDFCytotherapy
December 2024
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address:
Background Aims: With novel therapies improving prognosis, the complications of multiple myeloma after multi-line treatment, particularly myelosuppression, have become a crucial determinant of long-term outcomes. Non-myeloablative allogeneic hematopoietic stem cell transplantation is a feasible option, but the transplant-related mortality rate remains high. Our study presents a relapsed/refractory multiple myeloma patient with a 9-year disease history.
View Article and Find Full Text PDFAntibodies (Basel)
November 2024
Singapore Immunology Network, Agency for Science, Technology and Research, Immunos Building, 8A Biomedical Grove, Singapore 138648, Singapore.
Background: B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome.
View Article and Find Full Text PDFExpert Rev Clin Immunol
December 2024
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Introduction: Besides cytokine release syndromes (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated HLH-like syndrome (IEC-HS) is increasingly recognized across CAR-T recipients. This emergent and fatal syndrome is difficult to separate from other disorders during the early phase, and urgently requires more integrated diagnostic and therapeutic frameworks.
Areas Covered: Existing literature has pointed out the potential role of unbridled proliferation of cytotoxic T lymphocytes, lymphopenia of natural killing cells, and hypercytokinemia in triggering the IEC-HS.
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