The perplexity and hope of adoptive T-cell therapy for soft tissue sarcoma / 中国肿瘤生物治疗杂志

@#[摘 要] 软组织肉瘤（soft tissue sarcoma, STS）是20岁以下人群恶性肿瘤死亡的5大原因之一，传统的治疗方法疗效不佳且患者耐受性差，而免疫治疗为攻克STS提供了新途径。STS细胞表面多种高免疫原性抗原可作为工程化T细胞的攻击靶点，过继细胞疗法（adoptive T-cell therapy，ACT）在STS中具有较大的应用潜力。靶向HER2的CAR-T细胞疗法和靶向NY-ESO-1的TCR-T细胞疗法分别在临床试验中产生了临床获益，但其疗效也受到肿瘤免疫微环境的影响。STS部分肿瘤抗原在正常组织也有表达，可被CAR-T或TCR-T细胞错误攻击而引起严重的毒副作用。为进一步增强ACT治疗STS的有效性和安全性，联合免疫检查点抑制剂的综合治疗、CAR-T设计中导入自杀基因等新治疗策略已进入STS的临床治疗。随着二代测序技术的进步，对STS各亚型免疫学性质有了更深入的研究，对免疫治疗在STS中的应用会更加“特异性”和“个体化”。

Current status and challenges of TCR-T therapy in solid tumor / 中国肿瘤生物治疗杂志

@#[Abstract] T cell receptors (TCR) are specifically expressed on T cell surface, which can recognize different tumor antigens to kill and scavenge cancerous cells. TCR-engineered T cells (TCR-T) therapy is to harbor TCR specific to tumor cells and modify the T cells with genetic engineering techniques to achieve the purpose of treating tumors after transfusion. Despite some achievements in TCR-T therapy, there are still some problems, such as treatment toxicity, limited T cell infiltration and antigen-specific deficiency and so on. So, the safety and effectiveness of TCR-T therapy need to be constantly optimized. Therefore，this paper summarizes the research status of TCR-T therapy for solid tumors in domestic and overseas, as well as the existing problems and countermeasures.

Current situation and challenges of T cell receptor-engineered T cells in anti-tumor therapy / 中国肿瘤生物治疗杂志

@#T cell receptor-engineered T cell (TCR-T) therapy is one of the hotspots in the field of cancer immunotherapy. Considerable achievements have been made since the first successful clinical trial in 2006. However, problems still remain in cytotoxicity, safety and persistence of TCR-T therapy despite the rapid development. Improving the immunosuppressive tumor microenvironment and enhancingchemotaxis, infiltration as well as activation of TCR-T cell will be the key to improve its anti-tumor effect. Neoantigens, which are highly tumor-specific and immunogenic,are the basis for safe and effective treatment and individualized cancer immunotherapy. Besides, infusion of less differentiated T cell subsets is also a reliable way to generate a long-lasting immune response. Here, combing with current research progress, we offer our perspectives on the current situation and challenges of TCR-T from the three aspects above.

A brief introduction of identification of tumor antigen-specific TCR gene / 中国免疫学杂志

Adoptive therapy with T cells modified by tumor antigen specific T cell receptor(TCR)gene become a research hotspot in tumor biotherapy.The generation of high-affinity TCR is a significant pre-condition for TCR-T therapy.In this review,we focus on the identification of tumor antigen-specific TCR genes,which based on RT-PCR,single cell RT-PCR and CDR3 length polymorphism analysis.

The Expression and Protective Efficacy of DNA Vaccine Encoding Antibodized hgp100 / 中国肿瘤生物治疗杂志

Objective: To investigate whether the plasmid ?1neo-hgp100 could be expressed and presented in vitro and could protect the immunized mice from B16F10 challenge in vivo. Methods: ?1neo-hgp100 plasmid was constructed in which the DNA sequence encoding hgp100 CTL epitope inserted into CDR3 of ?1-neo vector. The expression of anti-bodized antigen and IFN-? in supernatant was measured by ELISA respectively after transfection J558L with ?1neo-hgp100 and further co-culture of J588L transfacted with ?1 neo-hgp100 and pmel TCR transgenic T cell. After introspleenic inoculation of ?1neo-hgp100, the protective efficacy of the gene vaccine was observed by means of measuring the tumor area every two days. Results: ?1neo-hgp100 could be expressed and presented in vitro, the immunogenecity of CTL epitope of hgp100 was strong enough and could activate gp100 specific T cell, the mice immunized with the gene vaccine could resist the tumor challenging in vivo. The mean survival time was prolonged to 36 days, compared to control group (P