Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTLs) can survive long-term as young memory T cells in vivo, with continuous tumor eradication. Banking of iPSCs as an unlimited "off-the-shelf" source of therapeutic T cells may be feasible. To generate safer iPSCs, we reprogrammed human papilloma virus type 16 (HPV16) E6-specific CTLs by Sendai virus vector without cotransduction of SV40 large T antigen. The iPSCs efficiently differentiated into HPV16-specific rejuvenated CTLs that demonstrated robust cytotoxicity against cervical cancer. The tumor-suppressive effect of rejuvenated CTLs was stronger and more persistent than that of original peripheral blood CTLs. These rejuvenated HPV16-specific CTLs provide a sustained tumor-suppressive effect even for epithelial cancers and constitute promising immunotherapy for cervical cancer.
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http://dx.doi.org/10.1016/j.ymthe.2020.07.004 | DOI Listing |
ACS Nano
May 2024
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Med-X Center for Materials, Sichuan University, Chengdu 610064, China.
Oncogene activation and epigenome dysregulation drive tumor initiation and progression, contributing to tumor immune evasion and compromising the clinical response to immunotherapy. Epigenetic immunotherapy represents a promising paradigm in conquering cancer immunosuppression, whereas few relevant drug combination and delivery strategies emerge in the clinic. This study presents a well-designed triune nanomodulator, termed ROCA, which demonstrates robust capabilities in tumor epigenetic modulation and immune microenvironment reprogramming for cancer epigenetic immunotherapy.
View Article and Find Full Text PDFCell Rep Med
December 2023
Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address:
Functionally rejuvenated human papilloma virus-specific cytotoxic T lymphocytes (HPV-rejTs) generated from induced pluripotent stem cells robustly suppress cervical cancer. However, autologous rejT generation is time consuming, leading to difficulty in treating patients with advanced cancer. Although use of allogeneic HPV-rejTs can obviate this, the major obstacle is rejection by the patient immune system.
View Article and Find Full Text PDFAdv Mater
November 2023
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.
The metabolic reprogramming of glioblastoma (GBM) poses a tremendous obstacle to effective immunotherapy due to its impact on the immunosuppressive microenvironment. In this work, a hydrogen-bonded organic framework (HOF) specifically designed for GBM immunotherapy is developed, taking advantage of the relatively isolated cholesterol metabolism microenvironment in the central nervous system (CNS). The HOF-based biotuner regulates extra/intracellular cholesterol metabolism, effectively blocking the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway and reducing 2B4 expression.
View Article and Find Full Text PDFStem Cell Res
December 2022
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:
In this study, we report a novel induced pluripotent stem cell (iPSC) line SYSUTFi001-A derived from cytotoxic T cells (CTLs) infiltrating in hepatocellular carcinoma (HCC), using an integrative Sendai virus vector. This pluripotent cell line shows a normal karyotype and can be redifferentiated to the rejuvenated CTLs targeted to HCC. The cell line SYSUTFi001-A can be further used to perform vitro and vivo anti-tumor assays and design future cell replacement therapies.
View Article and Find Full Text PDFRinsho Ketsueki
October 2022
Department of Hematology, Juntendo University School of Medicine.
Epstein-Barr virus (EBV)-associated lymphomas are common in Asia and exhibit a poor prognosis. As EBV antigens LMP1 and LMP2 are often expressed in EBV-associated lymphomas, these lymphomas should be a good target for antigen-specific cytotoxic T lymphocyte (CTL) therapy. However, CTLs continuously exposed to viral or tumor antigens often become exhausted.
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