دورية أكاديمية
أعرض في EDS

Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.

التفاصيل البيبلوغرافية
العنوان: Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.
المؤلفون: Lin M; Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore., Bhakdi SC; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.; X-Zell, Singapore., Tan D; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore., Lee JJX; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.; Oncology Academic Programme, Duke-NUS Medical School, Singapore., Tai DWM; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.; Oncology Academic Programme, Duke-NUS Medical School, Singapore., Pavesi A; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.; Mechanobiology Institute, National University of Singapore, Singapore., Wai LE; Lion TCR Pte Ltd, Singapore., Wang T; Lion TCR Pte Ltd, Singapore., Bertoletti A; Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore., Tan AT; Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
المصدر: Immunotherapy advances [Immunother Adv] 2023 Aug 14; Vol. 3 (1), pp. ltad015. Date of Electronic Publication: 2023 Aug 14 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101776979 Publication Model: eCollection Cited Medium: Internet ISSN: 2732-4303 (Electronic) Linking ISSN: 27324303 NLM ISO Abbreviation: Immunother Adv Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Oxford] : Oxford University Press, [2021]-
مستخلص: Recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated by the immunosuppressants required to prevent graft rejection. To circumvent the effects of immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T cells (IDRA HBV-TCR). However, their ability to eliminate HBV-HCC circulating in the whole blood has never been tested, and whether their lytic efficacy is compatible with the number of adoptively transferred T cells in vivo has never been measured. Hence, we developed a microscopy-based assay to quantify CTCs in whole blood. The assay was then used to quantify the efficacy of IDRA HBV-TCRs to lyse free-floating HBV-HCC cells in the presence of Tacrolimus and Mycophenolate Mofetil (MMF). We demonstrated that a panel of antibodies (AFP, GPC3, Vimentin, pan-Cytokeratin, and CD45) specific for HCC tumour antigens and immune cells can effectively differentiate HCC-CTCs in whole blood. Through dose-titration experiments, we observed that in the presence of immunosuppressive drugs, a minimum of 20 000 IDRA HBV-TCR T cells/ml of whole blood is necessary to lyse ~63.5% of free-floating HBV-HCC cells within 16 hours. In conclusion, IDRA HBV-TCR T cells can lyse free-floating HBV-HCC cells in whole blood in the presence of Tacrolimus and MMF. The quantity of IDRA-HBV TCR T cells required can be achieved by the adoptive transfer of 5 × 10 6 IDRA-HBV TCR-T cells/kg, supporting the utilisation of IDRA HBV-TCR T cells to eliminate CTCs as prophylaxis against recurrence after LT.
Competing Interests: S.C.B. owns stock in and receives compensation from X-Zell, a company owning patents and commercialising technologies covering rare-cell detection and characterisation. A.P. is a consultant and shareholder of AIM Biotech Pte. Ltd. A.B. and A.T.T. are the Scientific Founder and the Scientific Consultant of Lion TCR Pte. Ltd, respectively, a biotech company developing T-cell receptors for the treatment of virus-related diseases and cancers. All other authors disclose no conflicts.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)
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فهرسة مساهمة: Keywords: HBV; TCR T cells; adoptive T-cell transfer; circulating tumour cells; hepatocellular carcinoma
تواريخ الأحداث: Date Created: 20230828 Latest Revision: 20230829
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10460197
DOI: 10.1093/immadv/ltad015
PMID: 37636242
قاعدة البيانات: MEDLINE
الوصف
تدمد:2732-4303
DOI:10.1093/immadv/ltad015