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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 | 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 |
| 4 | 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 |
| 5 | Maximum Genus of Strong Embeddings显示文摘The strong embedding conjecture states that any 2-connected graph has a strong embedding on some surface. It implies the circuit double cover conjecture: Any 2-connected graph has a circuit double cover.Conversely, it is not true. But for a 3-regular graph, the two conjectures are equivalent. In this paper, a characterization of graphs having a strong embedding with exactly 3 faces, which is the strong embedding of maximum genus, is given. In addition, some graphs with the property are provided. More generally, an upper bound of the maximum genus of strong embeddings of a graph is presented too. Lastly, it is shown that the interpolation theorem is true to planar Halin graph. | Er-lingWei Yan-peiLiu HanRen | 2003 | Acta Mathematicae Applicatae Sinica2003，19，3： | 2 |
| 6 | Optimal model establishment of whole-process management data for CAR-T therapy in China—how should this be done?显示文摘Chimeric antigen receptor(CAR)T-cell therapy utilizes patients’own T lymphocytes that are engineered to attack cancer cells[1,2,3].With the US Food and Drug Administration(FDA)approval of four CD19-and one BCMA-targeted CAR therapy for B cell malignancies[4,5],CAR T-cell therapy has finally reached the status of a medicinal product. | Xiaolei Li Hanren Dai Xian Li Ping Li Wenbin Qian Aibin Liang Weidong Han | 2022 | Cellular & Molecular Immunology2022，19，1： | 2 |
| 7 | Cucurbit[8]uril-mediated multi-color fluorescence system for time-dependent information encryption显示文摘Programming microscopic assembly mode to control macroscopic property is an attractive research objective.In particular,controlling molecular assembly to control fluorescence is of considerable interest for developing smart fluorescent materials.Herein,a color-tunable supramolecular emissive system was developed based on cucurbit[8]uril mediated host-guest assembly.Chemical designing for the molecular structures with minimized change resulted in different assembly modes and hence generating distinctive fluorescence,including green,yellow and orange with the addition of cucurbit[n]uril.Taking advantage of this feature,the advanced information encryption material(4D code)with multiple encryption levels and time-dependent encryption feature was developed.Such a code was dynamic on time scale,generating a series of 3D codes with time.The encrypted information only can be recognized by integrating time-coursed codes.This work provides a new insight for designing intelligent fluorescent materials for information encryption with high level of security. | Biyan Lin Qian Wang Zhen Qi Hanren Xu Da-Hui Qu | 2023 | Science China Chemistry2023，66，4： | 1 |
| 8 | Performance prediction and design ofPBCF 显示文摘 | HU Zhian ZHOU Hanren | 1991 | Hydrodynamics Version A1991，6，3： | 1 |
| 9 | Growth of Human Colorectal Cancer SW1116 Cells Is Inhibited by Cytokine-Induced Killer Cells显示文摘 | Yao Wang Hanren Dai Hong Li Haiyan Lv Tao Wang Xiaobing Fu Weidong Han Ronald Herberman | 2010 | Clinical and Developmental Immunology2010，，： | 1 |
| 10 | Exploring innate immunity in cancer immunotherapy: opportunities and challenges显示文摘The recognition of the important role of cancer immunity in tumors has led to the introduction of immunotherapeutic strategies. Most of the immunomodulatory approaches currently being developed engage the adaptive immune system. The clinical approval of checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy has led to considerable success in treating hematologic malignancies.1,2,3,4 However, for the majority of patients with solid tumors, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells and interactions between tumor cells and all other cells in the local microenvironment of solid tumors. A large proportion of immune cells in and around solid tumors derive from the innate arm of the immune system, and using these innate cells against tumors offers an alternative immunotherapeutic option, while current strategies mainly focus on the adaptive arm of the immune system.5 In a recent issue of Cell research, Lv et al.6 discovered that Mn2+ played a critical role in the innate immune sensing of tumors, as Mn-insufficient mice poorly controlled tumor growth and metastasis. Mechanistically, Mn2+ promoted dendritic cell (DC) and macrophage maturation and tumor-specific antigen presentation, augmented CD8+ T-cell differentiation and activation and NK cell activation, and increased memory CD8+ T cells in a cyclic-AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent manner, uncovering a critical role of Mn in bridging innate and adaptive immunity for tumor surveillance. | Xiaolei Li Hanren Dai Hua Wang Weidong Han | 2021 | Cellular & Molecular Immunology2021，18，6： | 0 |
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