1.Anticancer effect of tea polyphenols on implanted breast cancer
Yan-Ming ZHANG ; Li XU ; Xin-Yi CHEN ; Neoplastic HEMATOLOGY ;
International Journal of Traditional Chinese Medicine 2006;0(06):-
Objective To observe the growth inhibiting effect of tea polyphenols on implanted mouse breast cancer(EMT_6),and offer the foundation for the next study on its inhibiting angiogenesis effect and its molecular mechanism.Methods Mammary adenocarcinoma EMT_6 was cultured and propagated,then implanted on female BALB/c mice.Tea polyphenols was peroral administrated and local injected.Anticancer function was determined with regular methods.Result After tea polyphenols were taken by oral and local injection on EMT_6 mammary adenocarcinoma mice,the inhibitory ratio of tumor are respectively 37.43% and 40.94%.Conclusion Tea polyphenols had significant inhibitive effect on implanted breast cancer.This offered the foundation for the next intensiVe study on its inhibiting angiogenesis effect and its molecular mechanism.
2.Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia.
Meng Yi DU ; Yan Qiang ZHANG ; Dan Ying LIAO ; Wei XIE ; Wei XIONG ; Heng MEI ; Yu HU
Chinese Journal of Hematology 2023;44(10):793-799
Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.
Animals
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Humans
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Mice
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Antigens, CD19
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Burkitt Lymphoma/drug therapy*
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Cell- and Tissue-Based Therapy
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Follow-Up Studies
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Immunotherapy, Adoptive
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Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy*
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
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Receptors, Chimeric Antigen