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-c...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.展开更多
BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consist...BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma(DLBCL).CASE SUMMARY We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide(50 mg per day)and an extended-release implant of goserelin(1/28 d).Seven years later,rectal DLBCL with lung metastases was found.CONCLUSION Although rare,the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.展开更多
The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by intervent...The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.展开更多
MicroRNAs (miRNAs) are posttranscriptional regulators fine-tuning the level of most messenger RNAs (mRNAs) and proteins in mammalian cells. Their expression is dysregulated in neoplastic cells and upregulated or downr...MicroRNAs (miRNAs) are posttranscriptional regulators fine-tuning the level of most messenger RNAs (mRNAs) and proteins in mammalian cells. Their expression is dysregulated in neoplastic cells and upregulated or downregulated miRNAs play an important role in tumorigenesis. Changes in the miRNA transcriptome appear to be suitable markers for the differential diagnosis of various B-cell lymphoma types and there are therapeutic attempts to normalize the expression level of key cellular miRNAs involved in lymphomagenesis. In this review we wish to outline the most recent developments in the application of sophisticated, chemically modified antisense oligonucleotides and their nanoparticle complexes to suppress oncogenic miRNAs. These advances form the basis of a new therapeutic approach that may complement current protocols for B-cell lymphoma therapy. Anti-cytokine therapy aiming at the removal of cytokines that activate key oncomirs, and switching on silenced tumor suppressor miRNAs by epigenetic drugs might also be considered, on the long run, in the treatment of well defined B-cell lymphoma types.展开更多
The clinical efficacy of chemotherapeutic drugs is hindered by their poor aqueous solubility, low bioavailability and severe side effects. In recent years, polymeric nanocarriers have been used for drug delivery to im...The clinical efficacy of chemotherapeutic drugs is hindered by their poor aqueous solubility, low bioavailability and severe side effects. In recent years, polymeric nanocarriers have been used for drug delivery to improve the efficacy of many chemotherapeutics. In this study, a series of biodegradable phenylalaninebased poly(ester amide)(Phe-PEA) with tunable molecular weights(MWs) were synthesized to systematically investigate the relationship between the polymer MW and the efficacy of the corresponding polymeric nanoparticles(NPs). The results indicated that a range of polymers with different MWs can be obtained by varying the monomer ratio or reaction time. Doxorubicin(DOX), a classic clinical lymphoma treatment strategy, was selected as a model drug. The loading capacity and stability of the higher MW polymeric NPs were superior to those of the lower MW ones. Moreover, in vitro and in vivo data revealed that high MW polymeric NPs had better anticancer efficacy against lymphoma and higher biosafety than low MW polymeric nanoparticles and DOX. Therefore, this study suggests the importance of polymer MW for drug delivery systems and provides valuable guidance for the design of enhanced polymeric drug carriers for lymphoma treatment.展开更多
Finding improved therapeutic protocols against non-Hodgkin’s lymphoma(NHL) remains an unmet clinical demand. Phototherapy is a promising alternative treatment for traditional clinical therapeutic methods, but the lim...Finding improved therapeutic protocols against non-Hodgkin’s lymphoma(NHL) remains an unmet clinical demand. Phototherapy is a promising alternative treatment for traditional clinical therapeutic methods, but the limited tissue penetration blocks the therapeutics. Inspired by the excellent physical and chemical properties of black phosphorus nanosheets(BPNSs), a fluorescence and thermal imaging guided photo-/sono-synergistic treatment platform BPNSs@PEG-SS-IR780/RGD is developed. This ingenious multifunctional theranostic platform not only exhibits outstanding photothermal conversion efficiency and highly efficient reactive oxygen species generation, but also has good biocompatibility, tumor-targeting and tumor microenvironment responsiveness. In addition, BPNSs@PEG-SS-IR780/RGD could actively target the tumor sites and generate excellent photothermal, photodynamic and sonodynamic therapeutic efficacy. Both in vitro and in vivo experiments indicate that BPNSs@PEG-SS-IR780/RGD can be a promising nanomaterial for NHL imaging and therapy. Taken together, this study not only expands the application field of black phosphorus materials, but also provides a possibility to design a new generation of NHL treatment regimens with clinical application potential.展开更多
Chimeric antigen receptor(CAR)T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma,mantle cell lymphoma,and follicular lymphoma,with multiple FDA-approved CAR ...Chimeric antigen receptor(CAR)T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma,mantle cell lymphoma,and follicular lymphoma,with multiple FDA-approved CAR T products now commercially available.Ongoing studies seek to move CAR T-cells to earlier lines of therapy and to characterize the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia.Other areas of active research address CAR T in combination with other lymphoma-directed therapies,and mechanisms of CAR T resistance.This review focuses on the FDA-approved anti-CD19 CAR T products for B-cell lymphomas,management of CAR T-cell-associated toxicities,approaches to bridging therapy,and ongoing clinical trials and future research directions across a broad range of lymphoma histologies.展开更多
Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin＇s lymphoma （NHL）. The main reason for poor prognosis is multidrug resistance （MDR）, for which the main phenotype is overexpres...Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin＇s lymphoma （NHL）. The main reason for poor prognosis is multidrug resistance （MDR）, for which the main phenotype is overexpression of P-glycoprotein （P-gp）. This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression. Methods Sixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression. Results In the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival （PFS） in the two groups （P=0.0651）, but the reversal agent group had a higher overall response rate （ORR） than did the control group （P=0.048）. Forty-one of 56 patients had P-gp（＋） tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed （CR＋CRu） reflecting a significant advantage in the reversal agent group （P=0.048）. Patients with P-gp（＋） tumor cells in the reversal agent group had a higher overall response rate （ORR） than did the control group （11/18 vs. 6/23, P=0.024）. Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp（＋） tumor cells in the reversal agent group had longer progression-free survival than did the control group （P=0.0464）. A small number of patients who received ligustrazine had a decrease in blood pressure. Conclusion Ligustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.展开更多
Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma(BCL)due to their reliable efficacy,manageable safety,high accessibility,and convenience for use.Still,no guidelines or con...Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma(BCL)due to their reliable efficacy,manageable safety,high accessibility,and convenience for use.Still,no guidelines or consensus focusing on oral drug therapies for BCL is available.To provide a reference of oral agent-based treatment for mature BCL,a panel of experts from the Lymphocyte Disease Group,Chinese Society of Hematology,Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China,combined with the latest authoritative guidelines in the world and current research reports.This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients.With the deepening of research and the development of standardized clinical applications,oral medications will bring better treatment to BCL patients,enabling more patients to benefit from them.展开更多
In recent years,Non-Hodgkin lymphoma(NHL)has been one of the most fast-growing malignant tumor diseases.NHL poses severe damages to physical health and a heavy burden to patients.Traditional therapies(chemotherapy or ...In recent years,Non-Hodgkin lymphoma(NHL)has been one of the most fast-growing malignant tumor diseases.NHL poses severe damages to physical health and a heavy burden to patients.Traditional therapies(chemotherapy or radiotherapy)bring some benefit to patients,but have severe adverse effects and do not prevent relapse.The relevance of emerging immunotherapy options(immune-checkpoint blockers or adoptive cellular methods)for NHL remains uncertain,and more intensive evaluations are needed.In this work,inspired by the idea of vaccination to promote an immune response to destroy tumors,we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties.In this vaccine,natural tumor cells are used as a vector to load CpG-ODN,and following lethal irradiation,the formulations were decorated with mannose.The study of the characterization of the doubleimproved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence,which displayed an antitumor function.In the lymphoma prevention model,the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency.Furthermore,unlike the non-improved vaccine,the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model.Next,to improve the moderate therapeutic effect of the mono-treatment method,we incorporated a chemotherapeutic drug(doxorubicin,DOX)into the process of vaccination and devised a combination regimen.Fortunately,a tumor inhibition rate of~85%was achieved via the combination therapy,which could not be achieved by mono-chemotherapy or mono-immunotherapy.In summary,the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.展开更多
Lymphoma is a diverse disease with a variety of different subtypes,each characterized by unique pathophysiology,tumor microenvironment,and underlying signaling pathways leading to oncogenesis.With our increasing under...Lymphoma is a diverse disease with a variety of different subtypes,each characterized by unique pathophysiology,tumor microenvironment,and underlying signaling pathways leading to oncogenesis.With our increasing understanding of the molecular biology of lymphoma,there have been a number of novel targeted therapies and immunotherapy approaches that have been developed for the treatment of this complex disease.Despite rapid progress in the field,however,many patients still relapse largely due to the development of drug resistance to these therapies.A better understanding of the mechanisms underlying resistance is needed to develop more novel treatment strategies that circumvent these mechanisms and design better treatment algorithms that personalize therapies to patients and sequence these therapies in the most optimal manner.This review focuses on the recent advances in therapies in lymphoma,including targeted therapies,monoclonal antibodies,antibody-drug conjugates,cellular therapy,bispecific antibodies,and checkpoint inhibitors.We discuss the genetic and cellular principles of drug resistance that span across all the therapies,as well as some of the unique mechanisms of resistance that are specific to these individual classes of therapies and the strategies that have been developed to address these modes of resistance.展开更多
The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that...The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified.Therapeutic agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients.However,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.Thus,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development.This review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.Additionally,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.展开更多
原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)是一种罕见的侵袭性结外非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL),主要累及脑、脊髓、软脑膜或玻璃体视网膜间隙,无系统受累证据。PCNSL约占中枢神经系统肿...原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)是一种罕见的侵袭性结外非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL),主要累及脑、脊髓、软脑膜或玻璃体视网膜间隙,无系统受累证据。PCNSL约占中枢神经系统肿瘤的4%,占所有NHL的4%~6%。与体部淋巴瘤相比,PCNSL的预后较差,五年生存率约为38.3%,十年生存率约30.5%。目前,PCNSL的最佳治疗方案尚未确定,以大剂量甲氨蝶呤(high-dose methotrexate,HD-MTX)为基础的联合化疗仍是推荐的一线治疗方法,常见的联合用药包括阿糖胞苷、利妥昔单抗、替莫唑胺等。随着对PCNSL分子机制及基因表型的深入探索,一些新药如BTK抑制剂(Bruton's tyrosine kinase inhibitor,BTKi)、免疫检查点抑制剂、核输出蛋白1(exportin 1,XPO-1)抑制剂等在淋巴瘤治疗领域令人瞩目的研究进展为PCNSL的治疗带来曙光,本文将对PCNSL的治疗现状与最新进展进行阐述。展开更多
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
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.
基金Supported by Key Research and Development Projects in Hebei Province,No.21377795DNatural Science Foundation of Hebei Province,No.H2021307017.
文摘BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma(DLBCL).CASE SUMMARY We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide(50 mg per day)and an extended-release implant of goserelin(1/28 d).Seven years later,rectal DLBCL with lung metastases was found.CONCLUSION Although rare,the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.
文摘The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.
文摘MicroRNAs (miRNAs) are posttranscriptional regulators fine-tuning the level of most messenger RNAs (mRNAs) and proteins in mammalian cells. Their expression is dysregulated in neoplastic cells and upregulated or downregulated miRNAs play an important role in tumorigenesis. Changes in the miRNA transcriptome appear to be suitable markers for the differential diagnosis of various B-cell lymphoma types and there are therapeutic attempts to normalize the expression level of key cellular miRNAs involved in lymphomagenesis. In this review we wish to outline the most recent developments in the application of sophisticated, chemically modified antisense oligonucleotides and their nanoparticle complexes to suppress oncogenic miRNAs. These advances form the basis of a new therapeutic approach that may complement current protocols for B-cell lymphoma therapy. Anti-cytokine therapy aiming at the removal of cytokines that activate key oncomirs, and switching on silenced tumor suppressor miRNAs by epigenetic drugs might also be considered, on the long run, in the treatment of well defined B-cell lymphoma types.
基金supported by the National Natural Science Foundation of China (Nos. 51973243 and 52173150)International Cooperation and Exchange of the National Natural Science Foundation of China (No. 51820105004)+3 种基金China Postdoctoral Science Foundation(No. 2020M683058)Shenzhen Science and Technology Program(No. RCBS20210706092411033)the Science and Technology Planning Project of Shenzhen (No. JCYJ20190807155801657)Guangdong Innovative and Entrepreneurial Research Team Program (No.2016ZT06S029)。
文摘The clinical efficacy of chemotherapeutic drugs is hindered by their poor aqueous solubility, low bioavailability and severe side effects. In recent years, polymeric nanocarriers have been used for drug delivery to improve the efficacy of many chemotherapeutics. In this study, a series of biodegradable phenylalaninebased poly(ester amide)(Phe-PEA) with tunable molecular weights(MWs) were synthesized to systematically investigate the relationship between the polymer MW and the efficacy of the corresponding polymeric nanoparticles(NPs). The results indicated that a range of polymers with different MWs can be obtained by varying the monomer ratio or reaction time. Doxorubicin(DOX), a classic clinical lymphoma treatment strategy, was selected as a model drug. The loading capacity and stability of the higher MW polymeric NPs were superior to those of the lower MW ones. Moreover, in vitro and in vivo data revealed that high MW polymeric NPs had better anticancer efficacy against lymphoma and higher biosafety than low MW polymeric nanoparticles and DOX. Therefore, this study suggests the importance of polymer MW for drug delivery systems and provides valuable guidance for the design of enhanced polymeric drug carriers for lymphoma treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.31971292,81871411,32011530115 and 32111540257)the Science&Technology Bureau of Ningbo City(Nos.2020Z094,2021Z072,2021J269)Ningbo Health Youth Technical Key Talents Training Project(No.rc2021011)。
文摘Finding improved therapeutic protocols against non-Hodgkin’s lymphoma(NHL) remains an unmet clinical demand. Phototherapy is a promising alternative treatment for traditional clinical therapeutic methods, but the limited tissue penetration blocks the therapeutics. Inspired by the excellent physical and chemical properties of black phosphorus nanosheets(BPNSs), a fluorescence and thermal imaging guided photo-/sono-synergistic treatment platform BPNSs@PEG-SS-IR780/RGD is developed. This ingenious multifunctional theranostic platform not only exhibits outstanding photothermal conversion efficiency and highly efficient reactive oxygen species generation, but also has good biocompatibility, tumor-targeting and tumor microenvironment responsiveness. In addition, BPNSs@PEG-SS-IR780/RGD could actively target the tumor sites and generate excellent photothermal, photodynamic and sonodynamic therapeutic efficacy. Both in vitro and in vivo experiments indicate that BPNSs@PEG-SS-IR780/RGD can be a promising nanomaterial for NHL imaging and therapy. Taken together, this study not only expands the application field of black phosphorus materials, but also provides a possibility to design a new generation of NHL treatment regimens with clinical application potential.
文摘Chimeric antigen receptor(CAR)T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma,mantle cell lymphoma,and follicular lymphoma,with multiple FDA-approved CAR T products now commercially available.Ongoing studies seek to move CAR T-cells to earlier lines of therapy and to characterize the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia.Other areas of active research address CAR T in combination with other lymphoma-directed therapies,and mechanisms of CAR T resistance.This review focuses on the FDA-approved anti-CD19 CAR T products for B-cell lymphomas,management of CAR T-cell-associated toxicities,approaches to bridging therapy,and ongoing clinical trials and future research directions across a broad range of lymphoma histologies.
基金This study was supported by a grant from the Province Natural Science Foundation of Shandong （No. Y2007C 148）.
文摘Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin＇s lymphoma （NHL）. The main reason for poor prognosis is multidrug resistance （MDR）, for which the main phenotype is overexpression of P-glycoprotein （P-gp）. This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression. Methods Sixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression. Results In the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival （PFS） in the two groups （P=0.0651）, but the reversal agent group had a higher overall response rate （ORR） than did the control group （P=0.048）. Forty-one of 56 patients had P-gp（＋） tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed （CR＋CRu） reflecting a significant advantage in the reversal agent group （P=0.048）. Patients with P-gp（＋） tumor cells in the reversal agent group had a higher overall response rate （ORR） than did the control group （11/18 vs. 6/23, P=0.024）. Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp（＋） tumor cells in the reversal agent group had longer progression-free survival than did the control group （P=0.0464）. A small number of patients who received ligustrazine had a decrease in blood pressure. Conclusion Ligustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.
文摘Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma(BCL)due to their reliable efficacy,manageable safety,high accessibility,and convenience for use.Still,no guidelines or consensus focusing on oral drug therapies for BCL is available.To provide a reference of oral agent-based treatment for mature BCL,a panel of experts from the Lymphocyte Disease Group,Chinese Society of Hematology,Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China,combined with the latest authoritative guidelines in the world and current research reports.This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients.With the deepening of research and the development of standardized clinical applications,oral medications will bring better treatment to BCL patients,enabling more patients to benefit from them.
基金financially supported by the National Natural Science Fund for Distinguished Young Scholar(NSFC31525009)National Natural Science Foundation of China(NSFC31930067,NSFC31771096,NSFC31871008,and NSFC31500809)+1 种基金the National Key Research and Development Program of China(2017YFC1103502)1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).
文摘In recent years,Non-Hodgkin lymphoma(NHL)has been one of the most fast-growing malignant tumor diseases.NHL poses severe damages to physical health and a heavy burden to patients.Traditional therapies(chemotherapy or radiotherapy)bring some benefit to patients,but have severe adverse effects and do not prevent relapse.The relevance of emerging immunotherapy options(immune-checkpoint blockers or adoptive cellular methods)for NHL remains uncertain,and more intensive evaluations are needed.In this work,inspired by the idea of vaccination to promote an immune response to destroy tumors,we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties.In this vaccine,natural tumor cells are used as a vector to load CpG-ODN,and following lethal irradiation,the formulations were decorated with mannose.The study of the characterization of the doubleimproved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence,which displayed an antitumor function.In the lymphoma prevention model,the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency.Furthermore,unlike the non-improved vaccine,the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model.Next,to improve the moderate therapeutic effect of the mono-treatment method,we incorporated a chemotherapeutic drug(doxorubicin,DOX)into the process of vaccination and devised a combination regimen.Fortunately,a tumor inhibition rate of~85%was achieved via the combination therapy,which could not be achieved by mono-chemotherapy or mono-immunotherapy.In summary,the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.
文摘Lymphoma is a diverse disease with a variety of different subtypes,each characterized by unique pathophysiology,tumor microenvironment,and underlying signaling pathways leading to oncogenesis.With our increasing understanding of the molecular biology of lymphoma,there have been a number of novel targeted therapies and immunotherapy approaches that have been developed for the treatment of this complex disease.Despite rapid progress in the field,however,many patients still relapse largely due to the development of drug resistance to these therapies.A better understanding of the mechanisms underlying resistance is needed to develop more novel treatment strategies that circumvent these mechanisms and design better treatment algorithms that personalize therapies to patients and sequence these therapies in the most optimal manner.This review focuses on the recent advances in therapies in lymphoma,including targeted therapies,monoclonal antibodies,antibody-drug conjugates,cellular therapy,bispecific antibodies,and checkpoint inhibitors.We discuss the genetic and cellular principles of drug resistance that span across all the therapies,as well as some of the unique mechanisms of resistance that are specific to these individual classes of therapies and the strategies that have been developed to address these modes of resistance.
基金supported in part by the National Institutes of Health Specialized Program of Research Excellence(SPORE)Grant CA070907 developmental awardThe University of Texas MD Anderson Cancer Center support Grant CA-016672+3 种基金endowed funds to The University of Texas MD Anderson Cancer Centerthe Moon Shots Programthe Homer Flower Research Fundthe Goldman Sachs Philanthropy Fund
文摘The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified.Therapeutic agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients.However,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.Thus,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development.This review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.Additionally,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.
