2017年8月7日 — 来自新加坡来恩公司的Antonio Bertoletti教授（科学创始人）和Sarene Koh博士（技术和生产部门总监），与来自德国汉堡大学医学中心的Maura Dandri教授和JanineKah博士，以及新加坡和德国多家机构，共同在《临床研究杂志》的7月期刊（请参阅新闻稿下方的JCI文章参考），发表了他们对于T细胞免疫疗法有效控制慢性乙型肝炎（CHB）感染的发现。CHB在HBV特异性T细胞反应中存在严重的定量和功能缺陷。HBV特异性T细胞的恢复是清除CHB病毒的决定性因素。该团队是首个使用mRNA转导技术，来工程改造瞬时HBV特异性TCR重定向的T细胞，作为抗CHB的新治疗策略的团队。该研究利用分子生物学技术来改造患者的T细胞。当TCR重新注入患者体内时，重定向的T淋巴细胞可以发现、识别和抑制或清除肝细胞中的乙型肝炎病毒。

‍

乙型肝炎是一种肝脏病毒感染，也是重大的全球健康问题。超过2.5亿人是慢性乙型肝炎（CHB）携带者，每年约有100万人死于与CHB相关的疾病。设计新的策略来消除和实现慢性HBV感染的功能性治愈成为了紧急需求。

‍

目前用于HCC的各种疗法只能抑制病毒，而无法清除病毒，患者继续面临并发症的危险，许多患者因此死亡。

‍

这项研究由杜克—国大、新加坡和德国多家著名机构以及来恩合作完成，为控制HBV感染、彻底清除HBV病毒以及治愈CHB提供了一种可能性与解决方案。这项研究使用了由Antonio Bertoletti教授发明的来恩专有技术TCR-T细胞疗法。 美通社

‍

JCI文章参考：

Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection.
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lutgehetmann, Antonio Bertoletti, and Maura Dandri. J Clin Invest. 2017 Aug1;127(8):3177-3188

‍

Abstract – Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice. We assessed virological and gene-expression changes using quantitative reverse-transcriptase PCR (qRT-PCR), immunofluorescence, and Luminex technology. HBV-specific T cells lysed HBV-producing hepatoma cells in vitro. In vivo, 3 injections ofHBV-specific T cells caused progressive viremia reduction within 12 days of treatment in animals reconstituted with haplotype-matched hepatocytes, whereas viremia remained stable in mice receiving irrelevant T cells redirected toward hepatitis C virus-specific TCRs. Notably, increases in alanine aminotransferase levels, apoptotic markers, and human inflammatory cytokines returned to pretreatment levels within 9 days after the last injection. T cell transfer did not trigger inflammation in uninfected mice. These data support the feasibility of using mRNA electroporation to engineer HBV TCR-redirected T cells inpatients with chronic HBV infection. PubMed

‍