新加坡– 2020年11月10日– 来恩于今日宣布，已在11月9日至14日举行的2020年度癌症免疫治疗学会（SITC）年度会议上发表了两个摘要。这些摘要重点展示了LioCyx-M的良好安全性和有效性，以及乙肝病毒特异性TCR-T细胞用于治疗乙肝病毒相关肝细胞癌的应用前景。

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TCR-T免疫疗法涉及对人体天然免疫T细胞进行生物工程重编程，以增强其对肿瘤细胞的溶细胞特异性功能。这些摘要中展示的临床数据支持了来恩龙头产品LioCyx-M用于原发性肝细胞癌（HCC）和肝移植后复发性肝细胞癌治疗的应用前景。

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摘要强调了来恩龙头产品LioCyx-M的良好安全性和有效性。LioCyx-M是经过体外修饰的，表达有乙型肝炎病毒（HBV）特异性T细胞受体的病人自体T细胞。LioCyx-M作为单一疗法，在两项独立的I期临床研究中，用于治疗不可切除的乙肝病毒相关肝细胞癌，以及肝移植后复发的肝细胞癌。这些数据显示出HBV特异性TCR-T细胞治疗方法，针对乙肝病毒相关肝细胞癌的治疗，具有良好的应用前景。

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有关会议海报的详细信息显示如下：

Title: Use of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Advanced HBV-related Hepatocellular Carcinoma (HCC)

‍Abstract #: 272

‍Co-corresponding authors: Antonio Bertoletti and Fu-Sheng Wang

‍Presenting Author: Fanping Meng

‍ClinicalTrials.gov number: NCT03899415

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‍Title: Phase I Study of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Recurrent HBV-Related Hepatocellular Carcinoma (HCC) Post-Liver Transplantation

‍Abstract #: 273

‍Co-corresponding authors: Antonio Bertoletti and Qi Zhang

‍Presenting Author: Jintao Cheng

‍ClinicalTrials.gov number: NCT02719782

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本新闻稿随附完整摘要。所附摘要已于2020年11月10日星期一美国东部时间上午8点在线发表在《癌症免疫治疗杂志》（JITC）上。

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点击这里:
Abstract 272: JITC在线文章
Abstract 273: JITC在线文章‍

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‍来恩生物医药有限公司简介
来恩生物医药有限公司是一家总部位于新加坡，处于临床研发阶段的生物科技公司，致力于开发T细胞受体（TCR）- T细胞疗法，以治疗亚洲地区广泛流行的威胁生命的病毒感染和病毒感染导致的癌症。

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龙头产品LioCyx-M简介
LioCyx-M是经过修饰可表达乙肝病毒特异性T细胞受体的自体T细胞，涵盖了不同种类的经过验证的衍生物。体内临床前研究和临床研究数据显示，这些经过修饰的T细胞能够标识，并且裂解乙肝病毒感染的肝细胞癌细胞(Koh et al, Mol. Ther. Nucleic Acids, 2013; Kah et al, J. Clin. Invest., 2017; Tan et al, Gastroenterology 2019).

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Abstract ID: 272

Use of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Advanced HBV-related Hepatocellular Carcinoma (HCC)

Fu-Sheng Wang1*, Fanping Meng1, Jiehua Jin 1, Yuanyuan Li 1, Regina Wanju Wong2, Anthony Tanoto Tan3, Tingting Wang2, Antonio Bertoletti2,3,4*
1Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
2Lion TCR Pte Ltd, Singapore
3Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
4Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore
*co-corresponding author

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Background
We have demonstrated the ability of Hepatitis-B-virus (HBV)-specific T cell receptor (TCR) bioengineered T cells to recognize and lyse Hepatocellular carcinoma (HCC) cells expressing HBV antigens derived from HBV-DNA integration in patients with liver transplant1.

LioCyx-M is an immunotherapeutic product composing of autologous T cells transiently modified with in-vitro transcribed mRNA encoding HBV-specific TCR. The transient TCR expression makes LioCyx -M amenable to a dose escalating posology.

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Methods
The primary endpoint of this Phase 1 trial is to assess the safety and tolerability of LioCyx-M in patients with advanced HBV-HCC without curative treatment options.

Eligible patients were diagnosed with Barcelona clinic liver cancer stage B or C HCC (Child-Pugh < 7 points), receiving >1 year antiviral treatment prior to enrollment. These patients had matching HLA class I genotypes which present HBV encoded antigen.

Peripheral blood was collected from each patient prior to each dose for LioCyx-M manufacturing. Patients received four escalating doses of 1×10E04 cells/kg, 1×10E05 cells/kg, 1×10E06 cells/kg, 5×10E06 cells/kg bodyweight (BW) in the first treatment cycle, each intravenously administered weekly.

Patients underwent one-month safety assessment post the fourth infusion, according to Common Terminology NCI CTCAE Version 4.0.3. If there were no dose associated toxicities, patients were eligible to continue administration of LioCyx-M at dose of 5 x10E06 cells/kg BW weekly. Tumor response per RECIST 1.1 criteria and survival time were assessed.

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Results
At data cutoff (30 April 2020), eight patients were enrolled, with a median age of 53 (range: 49 – 67). These patients received a median number of six (range: 4 – 12) infusions of LioCyx-M.

One patient developed Grade 3 elevations in alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and bilirubin after receiving LioCyx-M at dose level of 1×10E05 cells/kg BW.

Another patient had Grade 1 transient fever after receiving LioCyx-M at dose level 5×10E06 cells/kg BW in the 4th, 5th and 6th infusions.

No treatment-related adverse events (trAEs) such as cytokine release syndrome or neurotoxicity were observed. No fatal trAEs were observed.

The median time to progression was 1.9 months (range: 0.2 – 9.5 months). The median overall survival was 34 months (range: 3 – 38.2 months).

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Conclusion
The encouraging clinical outcome and tolerable safety highlight the good benefit-risk profile of LioCyx-M. Therefore, further exploration of efficacy of LioCyx-M treatment for advanced HBV-HCC is warranted in a Phase 2 proof-of-concept clinical study. Funding: Lion TCR. Clinical trial information: NCT03899415

1. Tan AT et al. Use of Expression Profiles of HBV DNA Integrated into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy, Gastroenterology. 2019; 156(6):1862-1876.e9 doi:https://doi.org/10.1053/j.gastro.2019.01.251.

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Abstract ID: 273

Phase I Study of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Recurrent HBV-Related Hepatocellular Carcinoma (HCC) Post-Liver Transplantation

Wenjie Chen1, Jintao Cheng1, Xiaofang Zheng1, Fan Yang1, Xiaofang Zheng1, Royce Fam2, Sarene Koh2,3, Lu-En Wai2,3, Tingting Wang2, Antonio Bertoletti2,3,4*, Qi Zhang1*
1Biotherapy Center, Third Affiliated Hospital, Sun Yat-Sen University
2Lion TCR Pte Ltd, Singapore
3Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore
4Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
*co-corresponding author

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Background
LioCyx-M is an immunotherapeutic product based on autologous T cells transiently modified with in vitro transcribed mRNA encoding HBV-specific T-cell receptors (TCR). We have previously shown, in a compassionate setting, the ability of LioCyx-M cells to recognize and lyse hepatocellular carcinoma (HCC) expressing HBV antigens derived from HBV-DNA integration in patients with HCC recurrence post-liver transplant1. Here, we report our Phase I study aimed to determine the feasibility, safety and preliminary efficacy of LioCyx-M in recurrent HBV-related HCC post-liver transplantation.

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Methods
Eligible patients with HBsAg-positive recurrent HCC as well as HLA-matched to selected TCRs were enrolled in this study.

All patients underwent leukapheresis prior to treatment and peripheral blood mononuclear cells (PBMC) were collected for LioCyx-M manufacturing.

During the first treatment cycle, patients received four escalating doses of 1×10E04 cells/kg, 1×10E05 cells/kg, 1×10E06 cells/kg, 5×10E06 cells/kg bodyweight (BW) intravenously every seven days. Adverse events were evaluated by Common Terminology Criteria for Adverse Events Version 4.0.

In the second treatment cycle, one infusion of LioCyx-M at dose of 1-5 x10E06 cells/kg BW was intravenously administrated every seven days for four weeks. The anti-tumour efficacy of LioCyx-M was evaluated per RECIST 1.1 criteria and survival was followed-up during the study.

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Results
Six patients were enrolled, with a median age of 35.5 (range: 28 – 47). These patients received a median number of 6.5 doses of LioCyx-M therapy (range: 4 – 12). Only fever was observed as treatment-related AEs. Grade 1 fever was observed at dose levels of 1 x 10E04 cells/kg BW (n=1) and 1-5 x 10E06 cells/kg BW (n=3) respectively. No cytokine release syndrome- and neurotoxicity-like AEs were observed.

Out of four patients evaluable for tumor response, the median of time to progression was at 1.3 months (range: 1.2 – 1.6 months). The median overall survival was 14 months (range: 4 – 22 months). At data cutoff (30 April 2020), one patient was still alive and five had passed on.

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Conclusion
Our data showed that multiple infusions of LioCyx-M are well tolerated at all dose levels administrated in recurrent HCC post liver transplantation, with no adverse effect to the transplanted liver. This calls for further assessment in a Phase 2 study. Funding: Lion TCR. Clinical trial information: NCT02719782

1. Tan AT et al. Use of Expression Profiles of HBV DNA Integrated into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy, Gastroenterology. 2019; 156(6):1862-1876.e9 doi:https://doi.org/10.1053/j.gastro.2019.01.251.