Diagnosis and treatment progress of primary central nervous system lymphoma / 白血病·淋巴瘤

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma type. The prognosis of PCNSL patients after treated by traditional therapy regimen is very poor. The way to evaluate the prognosis of PCNSL and to increase therapeutic efficacy have become the clinical problem. The 64th American Society of Hematology (ASH) annual meeting reported the latest research progress of diagnosis and treatment of PCNSL, including image examination, genetic sequencing, targeted therapy, chimeric antigen receptor T-cell (CAR-T) therapy and autologous hematopoietic stem cell transplantation (ASCT). This paper reviews the latest progress of PCNSL in the 64th ASH annual meeting.

Successful treatment of CD 19 targeted chimeric antigen receptor T cells in 2 children with isolated testicular recurrence of acute B lymphoblastic leukemia and literature review / 中华实用儿科临床杂志

This study reports the diagnosis and treatment of 2 children with isolated testicular recurrence (ITR) of acute B lymphoblastic leukemia (B-ALL) treated with CD 19 targeted chimeric antigen receptor T (CD 19 CAR-T) cells in May and December 2019 in the Department of Hematology and Oncology, Children′s Hospital of Soochow University, and explores the efficacy of CD 19 CAR-T cells therapy versus conventional radiotherapy and chemotherapy through literature review.Both cases were diagnosed as B-ALL by the morphologic, immunologic, cytogenetic and molecular biology methods.ITR was diagnosed by testicular biopsy at 60 months and 38 months after initial diagnosis in 2 cases, respectively.After infusion of CD 19 CAR-T cells at 7.0×10 6/kg and 1.5×10 7/kg, respectively for 7-10 days, testicular leukemia cell infiltration disappeared and complete remission was obtained.Among them, case 2 developed cytokine release syndrome and immune effector cell-related neurotoxicity syndrome after treatment, which was improved after drug intervention.It is suggested that CD 19 CAR-T cells are effective in the treatment of ITR in children, which may be an alternative to orchiectomy or local radiotherapy for ITR in children with B-ALL.

Preparation of CD52-targeted chimeric antigen receptor-modified T cells and their anti-leukemia effects / 中华血液学杂志

Objective: To construct chimeric antigen receptor (CAR) T cells targeting CD52 (CD52 CAR-T) and validate the effect of CD52 CAR-T cells on CD52-positive leukemia. Methods: A second-generation CD52-targeting CAR bearing 4-1BB costimulatory domain was ligated into a lentiviral vector through molecular cloning. Lentivirus was prepared and packaged by 293 T cells with a four-plasmid system. Fluorescein was used to label cell surface antigens to evaluate the phenotype of CD52 CAR-T cells after infection. Flow cytometry and ELISA were used to evaluate the specific cytotoxicity of CD52 CAR-T cells to CD52-positive cell lines in vitro. Results: ①A pCDH-CD52scFv-CD8α-4-1BB-CD3ζ-GFP expressing plasmid was successfully constructed and used to transduce T cells expressing a novel CD52-targeting CAR. ②On day 6, CD52-positive T cells were almost killed by CD52-targeted CAR-T post lentivirus transduction [CD52 CAR-T (4.48 ± 4.99) %, vs Vector-T (56.58±19.8) %, P=0.011]. ③T cells transduced with the CAR targeting CD52 showed low levels of apoptosis and could be expanded long-term ex vivo. ④The CD52 CAR could promote T cell differentiation into central and effector memory T cells, whereas the proportion of T cells with a CD45RA(+) effector memory phenotype were reduced. ⑤CD52 CAR-T cells could specifically kill CD52-positive HuT78-19t cells but had no killing effect on CD52-negative MOLT4-19t cells. For CD52 CAR-T cells, the percentage of residual of HuT78-19t cells was (2.66±1.60) % at an the E:T ratio of 1∶1 for 24 h, while (56.66±5.74) % of MOLT4-19t cells survived (P<0.001) . ⑥The results of a degranulation experiment confirmed that HuT78-19t cells significantly activated CD52 CAR-T cells but not MOLT4-19t cells[ (57.34±11.25) % vs (13.06± 4.23) %, P<0.001]. ⑦CD52 CAR-T cells released more cytokines when co-cultured with HuT78-19t cells than that of vector-T cells [IFN-γ: (3706±226) pg/ml, P<0.001; TNF-α: (1732±560) pg/ml, P<0.01]. Conclusions: We successfully prepared CD52 CAR-T cells with anti-leukemia effects, which might provide the foundation for further immunotherapy.

Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM).@*METHODS@#The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated.@*RESULTS@#After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity.@*CONCLUSION@#BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

The level of regulatory T lymphocyte detected by flow cytometry in chimeric antigen receptor T cell immunotherapy and its clinical significance / 中华检验医学杂志

Objective:To investigate the characteristics of changes in peripheral blood regulatory T lymphocyte (Treg) levels in patients with B-cell lymphoma who received chimeric antigen receptor (CAR)-T cell immunotherapy, and the relationship between Treg levels and optimal efficacy and treatment response.Methods:The data of 23 patients with relapsed/refractory B-cell malignancies who received CD19/CD22 CAR-T cell immunotherapy in Wuhan Tongji Hospital from 2019 to 2021 were retrospectively studied. The enrolled patients were divided into complete remission (CR) group (8 cases), partial remission (PR) group (7 cases) and no response(NR) group (8 cases) according to Lugano′s revised lymphoma efficacy evaluation criteria. A total of 16 patients with B-cell lymphoma who did not receive CAR-T cell immunotherapy during the same period in Wuhan Tongji Hospital were collected as the control group.In different periods during CAR-T cell immunotherapy, multicolor flow cytometry(MFC) was used to dynamically detect peripheral blood the proportion of Treg in CD4 +T cells (Treg/CD4 +T), the proportion of lymphocytes (Treg/Lym), the proportion of Treg in white blood cells (Treg/WBC), and the absolute number of Treg (Treg#). The trend of Treg levels over time, as well as the differences in Treg levels in patients with different prognosis groups in different periods were analyzed.According to the proportion of Treg and the median level of absolute number within 1 to 15 days after CAR-T cell infusion, the patients were divided into a low-level group with 11 cases and a high-level group with 12 cases. The statistical differences in the peak value of CAR-T copy, iron protein, and IL-6 were compared between various groups. Independent samples t test, Mann-Whitney U test, Cox-Stuart trend existence test and one-way analysis of variance was used in statistical analysis. Results:In the 23 patients who received CAR-T cell immunotherapy, the mean values of Treg/CD4 +T and Treg/Lym before CAR-T cell infusion were (20.42±7.96)% and (13.61±7.13)%, respectively, which were significantly higher than that of the control group [(7.33±3.61)%, t=5.893, P<0.001; (1.91±0.90)%, t=6.53, P<0.001]. The number of Treg in the meantime was significantly lower [(1.81±1.52)/μl<(13.66±9.89)/μl, t=4.261, P<0.001]. After infusion, Treg/CD4 +T and Treg/Lym all remarkably decreased ( P<0.001),Treg/WBC increased significantly( P=0.01). The mean values of Treg/CD4 +T (12.87±1.93)%, Treg/Lym (6.35±2.84)%, and Treg/WBC (0.05±0.05)% in the patients with CR as the best response group were lower than those in the PR group [(29.68±5.49)%( P<0.01), (21.85±2.1)%( P<0.01), 0.50±0.69( P<0.05)] before CAR-T cell immunotherapy. Patients with lower mean Treg/CD4 +T within 1 to 15 days after reinfusion of CAR-T cells had higher peak CAR-T copy number ( P<0.05). Conclusion:Treg/CD4 +T and Treg/Lym were increased and then decreased during CAR-T treatment in B cell malignancies. The patients with lower proportions of Treg before infusion have favorable treatment efficacy. Besides, patients with lower Treg/CD4 +T after infusion have better CAR-T cell expansion. In the process of CAR-T cell immunotherapy, the use of MFC to dynamically monitor the proportion of Treg has certain clinical significance for the prediction of the optimal efficacy of immunotherapy and the prediction of treatment response.

Effects of sodium iodide symporter co-expression on proliferation and cytotoxic activity of chimeric antigen receptor T cells in vitro / 南方医科大学学报

OBJECTIVE@#To investigate the effects of co-expression of sodium iodide symporter (NIS) reporter gene on the proliferation and cytotoxic activity of chimeric antigen receptor (CAR)-T cells in vitro.@*METHODS@#T cells expressing CD19 CAR (CAR-T cells), NIS reporter gene (NIS-T cells), and both (NIS-CAR-T cells) were prepared by lentiviral infection. The transfection rates of NIS and CAR were determined by flow cytometry, and the cell proliferation rate was assessed using CCK-8 assay at 24, 48 and 72 h of routine cell culture. The T cells were co-cultured with Nalm6 tumor cells at the effector-target ratios of 1∶2, 1∶1, 2∶1 and 4∶1 for 24, 48 and 72 h, and the cytotoxicity of CAR-T cells to the tumor cells was evaluated using lactate dehydrogenase (LDH) assay. ELISA was used to detect the release of IFN-γ and TNF-β in the co-culture supernatant, and the function of NIS was detected with iodine uptake test.@*RESULTS@#The CAR transfection rate was 91.91% in CAR-T cells and 99.41% in NIS-CAR-T cells; the NIS transfection rate was 47.83% in NIS-T cells and 50.24% in NIS- CAR-T cells. No significant difference in the proliferation rate was observed between CAR-T and NIS-CAR-T cells cultured for 24, 48 or 72 h (P> 0.05). In the co-cultures with different effector-target ratios, the tumor cell killing rate was significantly higher in CAR-T group than in NIS-CAR-T group at 24 h (P < 0.05), but no significant difference was observed between the two groups at 48 h or 72 h (P>0.05). Higher IFN-γ and TNF-β release levels were detected in both CAR-T and NIS-CAR-T groups than in the control group (P < 0.05). NIS-T cells and NIS-CAR-T cells showed similar capacity of specific iodine uptake (P>0.05), which was significantly higher than that in the control T cells (P < 0.05).@*CONCLUSION@#The co-expression of the NIS reporter gene does not affect CAR expression, proliferation or tumor cell-killing ability of CAR-T cells.

Chimeric Antigen Receptor T Cells Therapy for the Treatment of B-lymphoblastic Hematologic Malignancy ：A Rapid Health Technology Assessment / 中国药房

OBJECTIVE：To eval uate the effectiveness ，safety and economy of chimeric antigen receptor T cells （CAR-T） therapy for the treatment of B-lymphoblastic hematologic malignancy ，and to provide evidence-based reference for clinical decision. METHODS：Rapid health technology assessment （HTA）was adopted. PubMed ，Embase，Cochrane Library ，CNKI，Wanfang databases and foreign HTA official websites were systematically searched during the inception-Mar. 20th，2021. After inclusion ， data extraction and quality evaluation of literatures according to the inclusion and exclusion criteria ，descriptive analysis was performed for the effectiveness ，safety and economy of CAR-T therapy for the treatment of B-lymphoblastic hematologic malignancy. RESULTS ：A total of 2 HTA reports ，5 systematic reviews/Meta-analysis ，and 5 economics studies were included. In terms of effectiveness ，CAR-T therapy showed good efficacy in the treatment of B-lymphoblastic hematologic malignancy ；overall remission rate （ORR）of CAR-T therapy in the treatment of acute lymphoblastic leukemia was more than 63.5％，and the complete remission rate （CR）was 77.1％（95％CI：62.8％-87.1％）；ORR of CAR-T therapy in the treatment of chronic lymphoblastic leukemia was 70.0％（95％CI：53.0％-80.0％），and the CR was 25.5％（95％CI：13.9％-42.1％）；ORR of CAR-T therapy in the treatment of B-cell lymphoma was more than 44.4％. In terms of safety ，the incidence of cytokine release syndrome was more than 20％ during the treatment of CAR-T therapy ，and 1/3 or more （9％ believed in some studies ）patients suffered from neurotoxicity ； the incidence of infection was 12.2％-33.3％，and the incidence of graft-versus-host disease was 23.4％（95％CI：8.6％-49.8％）. In terms of economy ，most of the included studies believed that CAR-T therapy possessed economic advantages ，which were the results of evaluation in developed countries such as the United States and Japan. CONCLUSIONS ：CAR-T，as a new product of treatment for hematological malignancy ，shows good effectiveness and low level of ADR ，which is basically controllable ；its economy needs to be further evaluated by relevant researches combined with domestic reality.

Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19) / 生物工程学报

Adoptive immunotherapy based on chimeric antigen receptor-modified T cells (CAR-T) is one of the most promising strategies to treat malignant tumors, but its application in solid tumors is still limited. Glypican-3 (GPC3) is a meaningful diagnostic, therapeutic, and prognostic biomarker for hepatocellular carcinoma (HCC). The second/third generation GPC3-targeted CAR-T cells are generated to treat HCC. In order to improve the therapeutic effect, we constructed a fourth-generation lentiviral vector to express GPC3 CAR, human interleukin-7 (IL-7) and CCL19. Then the lentiviral vector and packaging plasmids were co-transfected into HEK293T cells to generate CAR lentiviral particles. Human T lymphocyte cells were transduced with CAR lentiviral to develop the fourth-generation GPC3-targeted CAR-T cells (GPC3-BBZ-7×19). In vitro, we used cell counting, transwell assay, luciferase bioluminescence assay and flow cytometry to compare the proliferation, chemotaxis, cytotoxicity and subtype distribution between GPC3-BBZ-7×19 CAR-T cells and the second generation GPC3-targeted CAR-T cells (GPC3-BBZ). In vivo, we established GPC3-positive HCC xenograft model in immunodeficient mice, then untransduced T cells (non-CAR-T) or GPC3-BBZ-7×19 CAR-T cells were injected. Tumor growth in mice was observed by bioluminescence imaging. Results showed that compared with GPC3-BBZ CAR-T, GPC3-BBZ-7×19 CAR-T cells had stronger proliferation, chemotactic ability, and higher composition of memory stem T cells (Tscm) (P values<0.05). However, there were no significant difference in cytotoxicity and cytokine secretion between them. In addition, GPC3-BBZ-7×19 CAR-T cells could significantly eliminate GPC3-positive HCC xenografts established in immunodeficient mice. Therefore, the fourth-generation GPC3-targeted CAR-T cells (secreting IL-7 and CCL19) are expected to be more durable and effective against HCC and produce tumor-specific memory, to provide a preclinical research basis for future clinical trials.

EGFR-CAR-T cells secreting PD-1 antibody significantly suppress the progression of gastric cancer / 中国肿瘤生物治疗杂志

@#[Abstract] Objective:To explore the anti-tumor effect of CAR-T cells secreting PD-1 scFv on gastric cancer. Method: We selected EGFR as the target of CAR-T cells and constructed second-generation EGFR-CAR-T cells (EGFR BB-z) and fourth-generation EGFR-CAR-T cells secreting PD-1 scFv (EGFR BB-z/E30). The anti-tumor activity was examined after in vitro activation and long-term stimulation, and its tumor suppression ability was validated through a mouse gastric cell xenograft model. Results: EGFR was highly expressed in gastric cancer tissues and cells (all P<0.01). EGFR BB-z and EGFR BB-z/E30 cells were successfully obtained by lentivirus infection. In vitro experiments showed that compared with EGFR BB-Z, EGFR BB-Z/E30 had longer long-term proliferation ability and stronger tumor killing activity (all P<0.01). In vivo experiments also validated that EGFR BB-z/E30 had obvious tumor inhibitory function in subcutaneous gastric tumor cell transplanted xenograft model and patient-derived tumor xenograft model (PDX) (all P<0.01). It also significantly increased T cell infiltration in tumor site and decreased the expression level of PD-1 (P<0.01 or P<0.05) on EGFR BB-z/E30 cell surface as well as the high secretion of IFN-γ (P<0.05). Conclusion: EGFR-CAR-T cell EGFR BB-z/E30 secreting PD-1 scFv can significantly inhibit the progression of gastric cancer and provide a potential new strategy for the treatment of gastric cancer.

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle cell lymphoma / 医学前沿

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.

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy / 医学前沿

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-γ, 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.

The evaluation of modified cell infusion method to reduce febrile non-hemolytic transfusion reaction in CD19 chimeric antigen receptor T cell threapy / 中华内科杂志

Objective@#To retrospectively analyze the efficacy and safety of modified cell infusion method in reducing the incidence of febrile non-hemolytic transfusion reaction (FNHTR).@*Methods@#A total of 69 patients were enrolled in the clinical trial of CD19 chimeric antigen receptor T (CAR-T) cell treatment from February 2017 to October 2018. Study group received the modified cell infusion method, that 1×106 CAR-T cells were re-suspended in 2 mg human serum albumin with total volume of 20 ml and injected intravenously. The control group was intravenously administrated with CAR-T cell in 100 ml normal saline. The incidence of FNHTR, cytokine releasing syndrome (CRS) grade, cytokine level and efficacy were compared.@*Results@#(1)The incidence of FNHTR in the study group was 21.1%, significantly lower than that in the control group (71%)(P=0.000). (2)There was no statistical difference in cell proliferation between the study group and the control group on day 4, 7, 14 and 21 after CAR-T cell infusion (P=10.223, 3.254, 5.551, 7.605). (3)There was no statistical difference in CRS grading between the study group and the control group (P=0.767). There was no statistical difference in the levels of interleukin 2 receptor (IL-2R), IL-6, tumor necrosis factor (TNF)-α between the two groups. (4)The C-reaction protein (CRP) level of the study group was lower than that of the control group on day 4 and 7 (P=0.026, 0.007). (5)There was no statistical difference of response rates in acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL) patients between the two groups (PALL=0.842; PNHL=0.866).@*Conclusion@#The modified cell infusion method in CD19 CAR-T cell treatment reduces the incidence of treatment-related FNHTR. It does not affect the proliferation of CAR-T cells in vivo, the grading of CRS and the response rates.

Immunotherapy precise targeting tumour microenvironment will become a key strategy of curing cancer / 中国肿瘤生物治疗杂志

@# The most two advanced development in cancer immunotherapy: (1) Infusion with in vitro activated or gene-modified T cells; (2) Activation of suppressive immune cells by antibodies to exert cytotoxicity. The first one about gene-modified T cells is mainly referred to chimeric antigen receptor-T cells (CAR-T) that have shown the significant efficacy in some haematological malignancies. The latter one about immune checkpoint blockades takes effects on tumors with burden of gene mutations. For cancer patients, however, tumor microenvironment is suppressed highly more than the systemic immune. Normalizing or enhancing the local microenvironment by systemic activation of immune response may cause the overreaction in other normal tissues, even severe damage, for example interstitial lung diseases, acute myocarditis, and severe liver failure. This review summarizes the characterization and classification of tumor immune microenvironment, development of cancer treatment and immunotherapy, and elucidates the importance of targeting tumor immune microenvironment. The key strategy is pointed out to efficiently and precision target tumor immune microenvironment by using self-secreting antibody CAR-T cells (baize T cells), quickly enhancing the immune function in tumor microenvironment, which may eventually cure cancer.

Homing barriers and solutions for CAR-T cells in the treatment of solid tumors / 中国肿瘤临床

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging immunotherapy that has allowed for major breakthroughs in the treatment of hematological neoplasms. However, little progress has been made in the treatment of solid tumors, primarily due to the difficulty in homing to tumor tissues by CAR-T cells during treatment. The complex tumor microenvironment and the barrier function of tumor tissues prevent CAR-T cells from contacting tumor cells, thereby preventing them from exerting their antitumor ac-tivity. This review article summarizes not only the progress made in the study of homing disorders of CAR-T cells in the treatment of solid tumors but also the current methods to overcome these disorders.

The evaluation of modified cell infusion method to reduce febrile non?hemolytic transfusion reaction in CD19 chimeric antigen receptor T cell threapy / 中华内科杂志

To retrospectively analyze the efficacy and safety of modified cell infusion method in reducing the incidence of febrile non?hemolytic transfusion reaction (FNHTR). Methods A total of 69 patients were enrolled in the clinical trial of CD19 chimeric antigen receptor T (CAR?T) cell treatment from February 2017 to October 2018. Study group received the modified cell infusion method, that 1×106 CAR?T cells were re?suspended in 2 mg human serum albumin with total volume of 20 ml and injected intravenously. The control group was intravenously administrated with CAR?T cell in 100 ml normal saline. The incidence of FNHTR, cytokine releasing syndrome (CRS) grade, cytokine level and efficacy were compared. Results (1)The incidence of FNHTR in the study group was 21.1%, significantly lower than that in the control group (71%)(P=0.000). (2)There was no statistical difference in cell proliferation between the study group and the control group on day 4, 7, 14 and 21 after CAR?T cell infusion (P=10.223, 3.254, 5.551, 7.605). (3)There was no statistical difference in CRS grading between the study group and the control group (P=0.767). There was no statistical difference in the levels of interleukin 2 receptor (IL?2R), IL?6, tumor necrosis factor (TNF)?α between the two groups. (4)The C?reaction protein (CRP) level of the study group was lower than that of the control group on day 4 and 7 (P=0.026, 0.007). (5)There was no statistical difference of response rates in acute lymphocytic leukemia (ALL) and non?Hodgkin lymphoma (NHL) patients between the two groups (PALL=0.842; PNHL=0.866). Conclusion The modified cell infusion method in CD19 CAR?T cell treatment reduces the incidence of treatment?related FNHTR. It does not affect the proliferation of CAR?T cells in vivo, the grading of CRS and the response rates.

Delayed Terminal Ileal Perforation in a Relapsed/Refractory B-Cell Lymphoma Patient with Rapid Remission Following Chimeric Antigen Receptor T-Cell Therapy / Journal of the Korean Cancer Association, 대한암학회지

Chimeric antigen receptor T-cell strategy targeting CD19 (CART19) has prominent anti-tumor effect for relapsed/refractory B-cell lymphomas. CART19-associated complications have been gradually recognized, however, late-onset complications have not been extensively studied. Herein, for the first time we report a diffuse large B-cell lymphoma patient with terminal ileum involvement obtained rapid remission and developed spontaneous terminal ileal perforation 38 days following CART19 infusion. The late-onset perforation reminds us that, for the safety of CART treatment, more cautions are warranted for the management of delayed GI complications.

Progress of CD123 chimeric antigen receptor T cells in treatment of acute myeloid leukemia / 白血病·淋巴瘤

Acute myeloid leukemia (AML) is the most common type of leukemia at present. Although clinical treatment has a certain effect on this disease, most patients still die of relapse or its treatment related diseases. Nowadays, chimeric antigen receptor (CAR) T cells therapy technology has developed rapidly, and has become a hot topic in tumor immunotherapy. The high expression of CD123 in AML cells, low expression or non expression in normal hematopoietic stem cells and tissues, make more and more researchers focus on the technology of CD123+cell immunotherapy. Some studies have confirmed that CD123 CAR-T cells have a certain effect on AML, which provides a new way for clinical treatment of relapsed or refractory AML. This review summarizes the structure, production and delivery methods of CD123 CAR-T cells, and the current research status and shortcomings of CD123 CAR-T cells.

Nursing of patients with B lymphocyte malignant tumor treated by CAR-T cell immunotherapy / 现代临床护理

Objective To summarize the experience of nursing the patients with B lymphocyte malignancies undergoing CAR-T cell immunotherapy. Method The nursing measures included nursing treatment and prognosis of 13 patients with B lymphocyte malignancies undergoing CAR-T cell immunotherapy at CAR-T cell transfusion, before and after transfusion. Results By careful treatment and care,11 of them were improved and discharged.2 cases complicated with severe CRS due to multiple organ failure,and died after rescue.There were no nursing related complications in 13 cases. Conclusion The nursing measures including full preparation,active nursing cooperation and effective treatment of complications are critical for the recovery of patients with B lymphocyte malignant tumor treated by CAR-T cell immunotherapy.

Efficacy improvement of chimeric antigen receptor T-cell immunotherapy: reports from the 57th American Society of Hematology annual meeting / 白血病·淋巴瘤

How to improve the efficacy of chimeric antigen receptor T-cell (CAR-T) is one of the key points for manufacture and application of CAR-T. In this review, the studies from the 57th American Society of Hematology (ASH) annual meeting regarding to the strategies for optimal CAR-T activity were summarized, including pathway inhibitors, enhancement antigen expression of target cells, optimization of conditioning chemotherapy, as well as the novel technology for CAR-T generation.

The research development of Chimeric Antigen Receptor T-cells in hematological malignancies / 实用肿瘤学杂志

In recent years,chimeric antigen receptor T -cells(CAR-T cells)therapy becomes the new rapid development of adoptive tumor immunotherapy .Its main characteristic is to identify specific T cell receptor of tumor antigen by genetic engineering modification and give its targeting ,killing and persistent treatment .The CAR-T was mentioned for the first time in 1989,and has developed to the fourth generation .CD19-CAR-T treatment technique shows activity in phase I clinical trials of multiple research centers .CAR-T therapy is ex-pected as a new way to cure relapse/refractory hematological malignancies .