دورية أكاديمية
أعرض في EDS

T cell receptor gene-modified allogeneic T cells with siRNA for endogenous T cell receptor induce efficient tumor regression without graft-versus-host disease.

التفاصيل البيبلوغرافية
العنوان: T cell receptor gene-modified allogeneic T cells with siRNA for endogenous T cell receptor induce efficient tumor regression without graft-versus-host disease.
المؤلفون: Okada S; Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Muraoka D; Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan., Yasui K; Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Tawara I; Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan., Kawamura A; Takara Bio Inc., Shiga, Japan., Okamoto S; Takara Bio Inc., Shiga, Japan., Mineno J; Takara Bio Inc., Shiga, Japan., Seo N; Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Mie, Japan.; Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan., Shiku H; Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Mie, Japan., Eguchi S; Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Ikeda H; Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
المصدر: Cancer science [Cancer Sci] 2023 Nov; Vol. 114 (11), pp. 4172-4183. Date of Electronic Publication: 2023 Sep 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Publishing on behalf of the Japanese Cancer Association Country of Publication: England NLM ID: 101168776 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1349-7006 (Electronic) Linking ISSN: 13479032 NLM ISO Abbreviation: Cancer Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: 2005- : Oxford : Wiley Publishing on behalf of the Japanese Cancer Association
Original Publication: Tokyo : Japanese Cancer Association, c2003-
مواضيع طبية MeSH: Neoplasms*/genetics , Graft vs Host Disease*/prevention & control , Hematopoietic Stem Cell Transplantation*, Mice ; Animals ; Humans ; RNA, Small Interfering/genetics ; Allogeneic Cells/metabolism ; Mice, SCID ; Receptors, Antigen, T-Cell ; Genes, T-Cell Receptor ; Immunotherapy, Adoptive
مستخلص: Adoptive immunotherapy using genetically engineered patient-derived lymphocytes to express tumor-reactive receptors is a promising treatment for malignancy. However, utilization of autologous T cells in this therapy limits the quality of gene-engineered T cells, thereby inhibiting the timely infusion of the cells into patients. In this study, we evaluated the anti-tumor efficacy and the potential to induce graft-versus-host disease (GVHD) in T cell receptor (TCR) gene-engineered allogeneic T cells that downregulate the endogenous TCR and HLA class I molecules with the aim of developing an "off-the-shelf" cell product with expanded application of genetically engineered T cells. We transduced human lymphocytes with a high-affinity TCR specific to the cancer/testis antigen NY-ESO-1 using a novel retrovirus vector with siRNAs specific to the endogenous TCR (siTCR vector). These T cells showed reduced expression of endogenous TCR and minimized reactivity to allogeneic cells in vitro. In non-obese diabetic/SCID/γc null mice, TCR gene-transduced T cells induced tumor regression without development of GVHD. A lentivirus-based CRISPR/Cas9 system targeting β-2 microglobulin in TCR gene-modified T cells silenced the HLA class I expression and prevented allogeneic CD8 + T cell stimulation without disrupting their anti-tumor capacity. This report is the first demonstration that siTCR technology is effective in preventing GVHD. Adoptive cell therapy with allogeneic T cells engineered with siTCR vector may be useful in developing an "off-the-shelf" therapy for patients with malignancy.
(© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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معلومات مُعتمدة: 21cm0106351h0003 Japan Agency for Medical Research and Development; 21H02990 Japan Society for the Promotion of Science
فهرسة مساهمة: Keywords: T cell receptor gene therapy; adoptive cell therapy; allogeneic cells; endogenous T cell receptor; human leukocyte antigen
المشرفين على المادة: 0 (RNA, Small Interfering)
0 (Receptors, Antigen, T-Cell)
تواريخ الأحداث: Date Created: 20230907 Date Completed: 20231113 Latest Revision: 20231113
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10637063
DOI: 10.1111/cas.15954
PMID: 37675556
قاعدة البيانات: MEDLINE
الوصف
تدمد:1349-7006
DOI:10.1111/cas.15954