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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

《医学前沿（英文）》 2019年 第13卷 第1期   页码 69-82 doi: 10.1007/s11684-018-0677-1

摘要：

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1157–165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-g and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.

关键词： cytokine-activated T cells     high-affinity T cell receptor     cancer immunotherapy     TCR-CAT    

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PtHAK5, a candidate for mediating high-affinity K

Haili YANG, Weidan ZHANG, Weiwei CHAI, Wenying WANG, Li GAO, Jing ZHANG, Yongping WANG, Suo-Min WANG

《农业科学与工程前沿（英文）》 2018年 第5卷 第1期   页码 108-117 doi: 10.15302/J-FASE-2018200

摘要： is a typical salt-exclu-ding halophytic grass with strong salt-tolerance, which enhances tolerance by restricting Na influx as well as having a strong selectivity for K over Na . The HAK5 K transporters generally modulate effective K acquisition in plants, especially under low K condition. In this study, from was isolated by RT-PCR and characterized using yeast complementation. The results showed PtHAK5 consisted of 784 amino acids and shared over 80% homology with the identified high-affinity K transporter HAK5 from other higher plants. The expression of rescued the K -uptake-defective phenotype of yeast strain CY162. In conclusion, PtHAK5 is a candidate for mediating high-affinity K uptake under low K conditions.

关键词： K+ uptake     PtHAK5     Puccinellia tenuiflora     yeast complementation    

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

《医学前沿（英文）》 2020年 第14卷 第6期   页码 701-710 doi: 10.1007/s11684-020-0763-z

摘要： Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

关键词： acute myeloid leukemia     CAR T     immunotherapy    

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A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 711-725 doi: 10.1007/s11684-020-0808-3

摘要： The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.

关键词： chimeric antigen receptor T (CAR-T) cell     lymphoma     cytokine release syndrome (CRS)     immune effector cell-associated neurotoxicity syndrome (ICANS)    

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Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphomaupon anti-CD19 chimeric antigen receptor T therapy

《医学前沿（英文）》 2023年 第17卷 第4期   页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment     tumor-associated macrophage     metabolism    

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Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse largeB-cell lymphoma in Chinese patients

《医学前沿（英文）》 2022年 第16卷 第2期   页码 285-294 doi: 10.1007/s11684-021-0843-8

摘要： Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade≥3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

关键词： CAR-T cell therapy     refractory diffuse large B-cell lymphoma     cytokine release syndrome     dose-limiting toxicity    

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Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

《医学前沿（英文）》 2019年 第13卷 第1期   页码 57-68 doi: 10.1007/s11684-019-0683-y

摘要：

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.

关键词： chimeric antigen receptor T cells     epidermal growth factor receptor     lung cancer     immunotherapy     tumor immunology    

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Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantlecell lymphoma

Ping Li, Ningxin Dong, Yu Zeng, Jie Liu, Xiaochen Tang, Junbang Wang, Wenjun Zhang, Shiguang Ye, Lili Zhou, Alex Hongsheng Chang, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 811-815 doi: 10.1007/s11684-020-0740-6

摘要： Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton’s tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin’s lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

关键词： anti-CD19 chimeric antigen receptor T cells     mantle cell lymphoma     relapsed or refractory     long-term follow-up    

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affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptorT cell therapy

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 786-791 doi: 10.1007/s11684-020-0751-3

摘要： Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis ( <0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

关键词： anti-CD19 chimeric antigen receptor T cell     soft tissue     bone marrow     relapsed or refractory non-Hodgkin lymphoma    

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Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 416-420 doi: 10.1007/s11684-012-0224-4

摘要：

Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL). In children, T-ALL usually has a worse prognosis than B-ALL, although childhood T-ALL prognoses have improved remarkably. The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance. Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor, which confers a much poorer prognosis than any other form of T-ALL. This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Flow cytometry data from T-ALL patients enrolled in Shanghai Children’s Medical Center between July 2002 and October 2010 were assessed according to Dr. Campana’s protocol. Among total 89 T-ALL cases, 74 cases had enough immunophenotype data available to differentiate between ETP (CD1a-, CD8-, CD5dim, at least one marker of stem cell or myeloid lineage) and non-ETP. From these 74 subjects, 12 ETP-ALL cases (16.2%) were identified. The event-free survival (EFS) rate at 66.8 months was 11.1%±10.1% for ETP-ALL and 57.6%±5.6% for non-ETP-ALL (P=0.003). The overall survival rates were 13.3%±11.0% for ETP-ALL and 64.7%±6.3% for non-ETP-ALL (P=0.002). Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis.

关键词： acute lymphoblastic leukemia     early T precursor     prognosis    

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Adoptive cell transfer therapy for hepatocellular carcinoma

Renyu Zhang, Zhao Zhang, Zekun Liu, Ding Wei, Xiaodong Wu, Huijie Bian, Zhinan Chen

《医学前沿（英文）》 2019年 第13卷 第1期   页码 3-11 doi: 10.1007/s11684-019-0684-x

摘要： Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.

关键词： adoptive cell transfer therapy     hepatocellular carcinoma     T cell     chimeric antigen receptor     immunotherapy    

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基于表位定向细胞库筛选高亲和力PD-1突变体诱骗分子 Article

刘昊, 乔春霞, 胡乃静, 王志宏, 王晶, 冯健男, 沈倍奋, 马远方, 罗龙龙

《工程（英文）》 2021年 第7卷 第11期   页码 1557-1565 doi: 10.1016/j.eng.2020.11.011

摘要：

抗程序性细胞死亡蛋白-1（programmed cell death protein-1,PD-1）/程序性细胞死亡配体-1（programmed cell death ligand-1, PD-L1）单克隆抗体的免疫疗法已成为治疗肺癌、肠癌和黑色素瘤等多种癌症的常规方法。PD-1/PD-L1信号通路在肿瘤微环境中可抑制T细胞活化，使其成为一个热门的抗癌靶点。野生型（wild type, WT）PD-1胞外结构域由于亲和力低而难以阻断PD-1/PD-L1复合物的形成。在MC38转基因小鼠模型中，463可有效逆转PD-1对T细胞活化的抑制作用，而且10 mg·kg−1的463突变体蛋白对肿瘤生长的抑制率约为75%，与同等剂量下

关键词： 诱饵程序性细胞死亡蛋白-1     程序性细胞死亡配体-1     哺乳动物细胞文库     表位定向    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

《医学前沿（英文）》 2022年 第16卷 第3期   页码 322-338 doi: 10.1007/s11684-021-0901-2

摘要： Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

关键词： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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从药物开发的角度看工程化T细胞疗法 Review

Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey

《工程（英文）》 2019年 第5卷 第1期   页码 140-149 doi: 10.1016/j.eng.2018.11.010

摘要： 例如，经基因修饰后，T 细胞可表达嵌合抗原受体（chimeric antigen receptor，CAR），使其能够识别并杀死肿瘤细胞，并形成一个记忆库，准备回击持续存在的恶性细胞。抗CD19 嵌合抗原受体T 细胞（CAR T cells，CART19）对某些恶性肿瘤具有显著的临床疗效。我们相信，就像胂凡纳明的发现开创了合成药物时代一样，CART19 的成功能够带来其他工程化T 细胞疗法的发展。

关键词： 工程化T细胞疗法     嵌合抗原受体     药物开发过程     生物标志物     CAR19     CART19    

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Deubiquitinases as pivotal regulators of T cell functions

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 451-462 doi: 10.1007/s11684-018-0651-y

摘要：

T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in T cell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs). DUBs are isopeptidases that cleave polyubiquitin chains and remove ubiquitin from target proteins, thereby controlling the magnitude and duration of ubiquitin signaling. It is now well recognized that DUBs are crucial regulators of T cell responses and serve as potential therapeutic targets for manipulating immune responses in the treatment of immunological disorders and cancer. This review will discuss the recent progresses regarding the functions of DUBs in T cells.

关键词： deubiquitinase     ubiquitination     T cell activation     T cell differentiation     T cell tolerance    

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标题 作者 时间 类型 操作

High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

期刊论文

PtHAK5, a candidate for mediating high-affinity K

Haili YANG, Weidan ZHANG, Weiwei CHAI, Wenying WANG, Li GAO, Jing ZHANG, Yongping WANG, Suo-Min WANG

期刊论文

Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

期刊论文

A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang

期刊论文

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphomaupon anti-CD19 chimeric antigen receptor T therapy

期刊论文

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse largeB-cell lymphoma in Chinese patients

期刊论文

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

期刊论文

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantlecell lymphoma

Ping Li, Ningxin Dong, Yu Zeng, Jie Liu, Xiaochen Tang, Junbang Wang, Wenjun Zhang, Shiguang Ye, Lili Zhou, Alex Hongsheng Chang, Aibin Liang

期刊论文

affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptorT cell therapy

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

期刊论文

Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia

null

期刊论文

Adoptive cell transfer therapy for hepatocellular carcinoma

Renyu Zhang, Zhao Zhang, Zekun Liu, Ding Wei, Xiaodong Wu, Huijie Bian, Zhinan Chen

期刊论文

基于表位定向细胞库筛选高亲和力PD-1突变体诱骗分子

刘昊, 乔春霞, 胡乃静, 王志宏, 王晶, 冯健男, 沈倍奋, 马远方, 罗龙龙

期刊论文

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

期刊论文

从药物开发的角度看工程化T细胞疗法

Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey

期刊论文

Deubiquitinases as pivotal regulators of T cell functions

null

期刊论文