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| 1 | 2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma显示文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS. | Ping Li Yang Liu Yun Liang Jian Bo Sujun Gao Yongxian Hu Yu Hu He Huang Xiaojun Huang Hongmei Jing Xiaoyan Ke Jianyong Li Yuhua Li Qifa Liu Peihua Lu Heng Mei Ting Niu Yongping Song Yuqin Song Liping Su Sanfang Tu Jianxiang Wang Depei Wu Zhao Wang Kailin Xu Zhitao Ying Qingming Yang Yajing Zhang Fengxia Shi Bin Zhang Huilai Zhang Xi Zhang Mingfeng Zhao Weili Zhao Xiangyu Zhao Liang Huang Jun Zhu Wenbin Qian Weidong Han Aibin Liang | 2023 | Cancer Biology & Medicine2023，20，2： | 3 |
| 2 | Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy显示文摘Despite the advancement of treatments,adults with relapsed/refractory(R/R)B-lineage acute lymphoblastic leukemia(B-ALL)have poor prognosis,with an expected five-year overall survival(OS)rate of 10%‒20%(Nguyen et al.,2008;Oriol et al.,2010).Extramedullary relapse of B-ALL is regarded as a highrisk factor generally associated with poor survival,occurring in about 15%to 20%of all relapsed patients(Ding et al.,2017;Sun et al.,2018).The central nervous system(CNS)and the testes are the most common sites of extramedullary relapse of B-ALL.In addition,extramedullary leukemia can appear in the skin,eyes,breasts,bones,muscles,and abdominal organs.The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation(allo-HSCT)is extremely poor(Spyridonidis et al.,2012;Dahlberg et al.,2019).Conventional chemotherapy or radiation is often ineffective in such patients.At present,there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT. | Delin KONG Tingting YANG Jia GENG Ruirui JING Qiqi ZHANG GuoqingWEI He HUANG Yongxian HU | 2022 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2022，23，10： | 2 |
| 3 | Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies:a phase I clinical study显示文摘Chimeric antigen receptor(CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts.Allogeneic CAR-T cells,generated from healthy donor T cells,can provide ready-to-use,blast-free therapeutic products,but their application could be complicated by graft-versus-host disease(GvHD)and host rejection.Here we developed healthy donor-derived,CD7-targeting CAR-T cells(RD13-01)with genetic modifications to resist fratricide,GvHD and allogeneic rejection,as well as to potentiate antitumor function.A phase I clinical trial(NCT04538599)was conducted with twelve patients recruited(eleven with T cell leukemia/lymphoma,and one with CD7-expressing acute myeloid leukemia).All patients achieved pre-set end points and eleven proceeded to efficacy evaluation.No dose-limiting toxicity,GvHD,immune effector cell-associated neurotoxicity or severe cytokine release syndrome(grade≥3)were observed.28 days post infusion,81.8%of patients(9/11)showed objective responses and the complete response rate was 63.6%(7/11,including the patient with AML).3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation.With a median follow-up of 10.5 months,4 patients remained in complete remission.Cytomegalovirus(CMV)and/or Epstein-Barr virus(EBV)reactivation was observed in several patients,and one died from EBV-associated diffuse large B-cell lymphoma(DLBCL).Expansion of CD7-negative normal T cells was detected post infusion.In summary,we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7^(+)hematological malignancies.Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7^(+)tumors. | Yongxian Hu Yali Zhou Mingming Zhang Houli Zhao Guoqing Wei Wengang Ge Qu Cui Qitian Mu Gong Chen Lu Han Tingting Guo Jiazhen Cui Xiaoyan Jiang Xiujun Zheng Shuhui Yu Xiaolong Li Xingwang Zhang Mingxi Chen Xiuju Li Ming Gao Kang Wang Cheng Zu Hao Zhang Xiaohong He Yanbin Wang Dongrui Wang Jiangtao Ren He Huang | 2022 | Cell Research2022，32，11： | 2 |
| 4 | An Efficient Summer Operation Scheme for a Thermal Power Plant Air Cooling System based on Electric Peak Shaving显示文摘We proposed a novel efficient operation scheme for a thermal power plant’s air-cooling system based on peak shaving, in order to cope with high ambient temperature in summer. We introduced an absorptiongeneration equipment with water/lithium working pairs into the air cooled condenser(ACC) to reconstruct the traditional thermal power plant, and established a dynamic thermodynamic model adopting Ebsilon code. We studied the thermodynamic performance variation of the reconstructed thermal power plant throughout a 24-hour cycle and found that the fluctuation ratio of the turbine back pressure decreased to 6% from 78%, which is beneficial for the stable and safe operation of the electric power system. The thermal performance improvement benefited from the exploitation of the heat transfer potential of ACC, which realized via cold duty schedule throughout the day, under different ambient temperature conditions. In this system, the generated power was higher at relatively high ambient temperature than that at relatively low ambient temperature, which solved the electricity demand-supply imbalance problem under high ambient temperature. Finally, the same optimization effects for power thermal plants with an indirect air-cooling system were obtained using the same operation scheme. | HU Hemin LIANG Shiqiang JIANG Yuyan GUO Yongxian | 2020 | Journal of Thermal Science2020，29，2： | 2 |
| 5 | Relapse after CAR-T cell therapy in B-cell malignancies: challenges and future approaches显示文摘Chimeric antigen receptor-T(CAR-T)cell therapy,as a novel cellular immunotherapy,has dramatically reshaped the landscape of cancer treatment,especially in hematological malignancies.However,relapse is still one of the most troublesome obstacles to achieving broad clinical application.The intrinsic factors and superior adaptability of tumor cells mark a fundamental aspect of relapse.The unique biological function of CAR-T cells governed by their special CAR construction also affects treatment efficacy.Moreover,complex cross-interactions among CAR-T cells,tumor cells,and the tumor microenvironment(TME)profoundly influence clinical outcomes concerning CAR-T cell function and persistence.Therefore,in this review,based on the most recent discoveries,we focus on the challenges of relapse after CAR-T cell therapy in B-cell malignancies from the perspective of tumor cells,CAR-T cells,and the TME.We also discuss the corresponding basic and clinical approaches that may overcome the problem in the future.We aim to provide a comprehensive understanding for scientists and physicians that will help improve research and clinical practice. | Tianning GU Meng ZHU He HUANG Yongxian HU | 2022 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2022，23，10： | 1 |
| 6 | A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma显示文摘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. | Houli Zhao Yiyun Wang Elaine Tan Su Yin Kui Zhao Yongxian Hu He Huang | 2020 | Frontiers of Medicine2020，14，6： | 0 |
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