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| 1 | Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer显示文摘The successes achieved by chimeric antigen receptor-modified T(CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer(NSCLC). In this phase I clinical study(NCT01869166), patients with epidermal growth factor receptor(EGFR)-positive(>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR+ T cells was 0.97×10~7 cells kg^(-1)(interquartile range(IQR), 0.45 to 1.09×10~7 cells kg^(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC. | Kaichao Feng Yelei Guo Hanren Dai Yao Wang Xiang Li Hejin Jia Weidong Han | 2016 | Science China(Life Sciences)2016，59，5： | 62 |
| 2 | Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers显示文摘 | Kaichao Feng Yang Liu Yelei Guo Jingdan Qiu Zhiqiang Wu Hanren Dai Qingming Yang Yao Wang Weidong Han1,3 | 2018 | Protein & Cell2018，9，10： | 37 |
| 3 | Cytokine-induced killer (ClK) cells:from basic research to clinical translation显示文摘The accumulation of basic researches and clinical studies related to cytokine-induced killer(CIK) cells has confirmed their safety and feasibility in treating malignant diseases.This review summarizes the available published literature related to the biological characteristics and clinical applications of CIK cells in recent years.A number of clinical trials with CIK cells have been implemented during the progressive phases of cancer,presenting potential widespread applications of CIK cells for the future.Furthermore,this review briefly compares clinical applications of CIK cells with those of other adoptive immunotherapeutic cells.However,at present,there are no uniform criteria or large-scale preparations of CIK cells.The overall clinical response is difficult to evaluate because of the use of autologous CIK cells.Based on these observations,several suggestions regarding uniform criteria and universal sources for CIK cell preparations and the use of CIK cells either combined with chemotherapy or alone as a primary strategy are briefly proposed in this review.Large-scale,controlled,grouped,and multi-center clinical trials on CIK cell-based immunotherapy should be conducted under strict supervision.These interventions might help to improve future clinical applications and increase the clinical curative effects of CIK cells for a broad range of malignancies in the future. | Yelei Guo Weidong Han | 2015 | Chinese Journal of Cancer2015，34，3： | 29 |
| 4 | Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment显示文摘 | Zhenguang Wang Yelei Guo Weidong Han | 2017 | Protein & Cell2017，8，12： | 24 |
| 5 | Clinical development of CAR T cell therapy in China:2020 update显示文摘Chimeric antigen receptor(CAR)T-cell therapy has achieved significant success in the treatment of hematological malignancies.In recent years,fast-growing CAR T clinical trials have actively explored their potential application scenarios.According to the data from the clinicaltrials.gov website,China became the country with the most registered CAR T trials in September 2017.As of June 30,2020,the number of registered CAR T trials in China has reached 357.In addition,as many as 150 other CAR T trials have been registered on ChiCTR.Although CAR T therapy is flourishing in China,there are still some problems that cannot be ignored.In this review,we aim to systematically summarize the clinical practice of CAR T-cell therapy in China.This review will provide an informative reference for colleagues in the field,and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation. | Jianshu Wei Yelei Guo Yao Wang Zhiqiang Wu Jian Bo Bin Zhang Jun Zhu Weidong Han | 2021 | Cellular & Molecular Immunology2021，18，4： | 11 |
| 6 | Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo显示文摘 | Yanjing Song Chuan Tong Yao Wang Yunhe Gao Hanren Dai Yelei Guo Xudong Zhao Yi Wang Zizheng Wang Weidong Han Lin Chen | 2018 | Protein & Cell2018，9，10： | 11 |
| 7 | An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T(CAR-T) cells显示文摘Anti-CD19 chimeric antigen receptor-modified T(CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines(mainly interleukin 6 and C-reactive protein) were identified in two patients(Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission. | Yajing Zhang Wenying Zhang Hanren Dai Yao Wang Fengxia Shi Chunmeng Wang Yelei Guo Yang Liu Meixia Chen Kaichao Feng Yan Zhang Chuanjie Liu Qingming Yang Suxia Li Weidong Han | 2016 | Science China(Life Sciences)2016，59，4： | 6 |
| 8 | Targeting cancer stem cells by using chimeric antigen receptor-modified T cells: a potential and curable approach for cancer treatment显示文摘 | Yelei Guo Kaichao Feng Yao Wang Weidong Han | 2018 | Protein & Cell2018，9，6： | 3 |
| 9 | Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment显示文摘(CAR)T cells and immune checkpoint blockade therapies has shown remarkable outcomes in the field of cancer treatment.1,2 In particular,great success has been achieved in B cell acute lymphocytic leukemia(B-ALL)treated with anti-CD19 CAR T cells.2 However,the loss,mutation,and reduced expression of CD19 are crucial causes for the failure of CAR T cell treatment in leukemia patients.3,4 CD38,a 45-kDa type II glycoprotein,is detectable in BALL,and several studies have indicated the efficacy and safety of CD38 monoclonal antibodies in clinical applications,suggesting that CD38 represents a suitable therapeutic target for the treatment of B-ALL.5,6 In addition,we developed a CAR against CD38,and our preclinical study indicated that anti-CD38 CAR T(CAR T-38)cells could specifically lyse CD38-positive tumor cells.7 Herein,we present the anti-leukemia ability of CAR T-38 cells in an adult relapsed B-ALL patient after failure of bi-specific CD19/CD22 CAR T cell treatment,and this administration of CAR T-38 cells was accompanied by the occurrence of target-mediated toxicities and severe and uncontrollable cytokine release syndrome(CRS). | Yelei Guo Kaichao Feng Chuan Tong Hejin Jia Yang Liu Yao Wang Dongdong Ti Qingming Yang Zhiqiang Wu Weidong Han | 2020 | Cellular & Molecular Immunology2020，17，4： | 1 |
| 10 | Characteristics of premanufacture CD8^(+) T cells determine CAR-T efficacy in patients with diffuse large B-cell lymphoma显示文摘Although chimeric antigen receptor(CAR)T cells have become an important treatment option for patients with relapsed/refractory B-cell malignancies,more than 60%of patients with diffuse large B-cell lymphoma(DLBCL)treated with CAR-T cell therapies fail to achieve a durable response.To reveal changes in CAR-T cell therapy and identify response biomarkers,we conducted a retrospective analysis of pre-manufacture source T cells and CAR-T cell products and their association with outcome in 58 patients with r/rDLBCL who received tandem CD19/CD20 CAR-T cell therapy.We performed bulk RNA-Seq,single-cell RNA-Seq,and paired T cell receptor sequencing on CAR-T cell products and pre-manufacture T cells from DLBCL patients.We note that a CD8+stem cell-like memory T cell population with a higher proportion and enhanced activating capacity of the CAR-T cell products was key to achieving durable clinical response.By analysing autologously-derived,pre-manufacture T cells,our data suggest that heterogeneity in the cellular and molecular features of pre-manufacture T cells contribute to the variation in efficacy after CAR-T cell therapy in DLBCL.The differences in anti-tumour efficacy of CAR-T cells among patients with different clinical outcomes appear to be due to the loss of CCR7 gene expression,coupled with increased expression of activation-and inhibitor-related genes in the CD8+naïve-T cell populations among the apheresis T cells from patients with a poor molecular response.These findings significantly advance our understanding of the underlying molecular determinants of pre-manufacture T cell function. | Yao Wang Chuan Tong Yuting Lu Zhiqiang Wu Yelei Guo Yang Liu Jianshu Wei Chunmeng Wang Qingming Yang Weidong Han | 2023 | Signal Transduction and Targeted Therapy2023，8，11： | 0 |
| 11 | Reciprocal activation of antigen-presenting cells and CAR T cells triggers a widespread endogenous anti-tumor immune response through sustained high-level IFNγproduction显示文摘Adoptive cell transfer(ACT)using chimeric antigen receptor(CAR)modified T cells and T cell receptor(TCR)engineered T cells has shown therapeutic efficacy in cancer treatment1,2.CAR T cells are widely applicable to tumor patients because of their ability to directly identify tumor cells in an MHCindependent manner. | Yelei Guo Chuan Tong Zhiqiang Wu Yuting Lu Yao Wang Weidong Han | 2023 | Cancer Biology & Medicine2023，20，11： | 0 |
| 12 | Identification of NOXA as a pivotal regulator of resistance to CAR T-cell therapy in B-cell malignancies显示文摘Despite the remarkable success of chimeric antigen receptor(CAR)T-cell therapy for treating hematologic malignancies,resistance and recurrence still occur,while the markers or mechanisms underlying this resistance remain poorly understood.Here,via an unbiased genome-wide CRISPR/Cas9 screening,we identified loss of NOXA,a B-cell lymphoma 2(BCL2)family protein in B-cell malignancies,as a pivotal regulator of resistance to CAR T-cell therapy by impairing apoptosis of tumor cells both in vitro and in vivo.Notably,low NOXA expression in tumor samples was correlated with worse survival in a tandem CD19/20 CAR T clinical trial in relapsed/refractory B-cell lymphoma. | Xin Yan Deyun Chen Yao Wang Yelei Guo Chuan Tong Jianshu Wei Yajing Zhang Zhiqiang Wu Weidong Han | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 0 |
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