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Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. The outcome of relapsed/refractory FL patients after multi-therapy is poor. The 64th American Society of Hematology annual meeting in 2022 announced the latest updates on relapsed/refractory FL, including targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell. This review provides an overview of these updates.
Résumé
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Although patients with FL generally have a good prognosis, the treatment of relapsed/refractory FL remains a challenge. The 63rd American Society of Hematology (ASH) Annual Meeting announced the latest updates on relapsed/refractory FL, including the usage of targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy. This article provides an overview of the updates in combination with the reports presented at the ASH Annual Meeting.
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Objective:To investigate the induction of specific T lymphocyte by bispecific monoclonal antibody in pancreatic cancer and its killing effects on KIF20A positive pancreatic cancer PANC1 cell line.Methods:CD 3/KIF20A bispecific monoclonal antibody was prepared and concentrated by chemical cross-linking method and purified by Sephrose-25 gel chromatography. Peripheral blood samples of healthy volunteers were collected, and monocytes were isolated using lymphocyte separation solution, and then cultured as dendritic cells (DC) and T cells respectively, and then co-cultured as DC-T cells. Meanwhile vitamin C was used to treat DC-T cells (vcDC-T cells). The levels of IFN-γ, IL-2, IL-4 and IL-12 in the supernatants and T cell subsets were detected by flow cytometry. About 1×10 5 T cells, DC-T cells, and vcDC-T cells with 10, 50, 100 and 300 ng CD 3/KIF20A antibody loaded were cocultured with PANC1 cells (20∶1) for 2, 6 and 10 hours to determine the highest killing rate dosage of CD 3/KIF20A antibody loaded cells. DC-T cells and DC-T cells, vcDC-T cells loaded with the highest killing rate dosage of CD 3/KIF20A antibody were cocultured with PANC1 cells (20∶1) for 2, 6, 8, 10 and 12 hours. The aggregation effect of effector cells on target cells was observed under inverted microscope, the killing rate of tumor cells was detected by LDH method. Results:The molecular weight of CD 3/KIF20A antibody was 130 000 measured and validated by SDS gel electrophoresis. The ratio of CD 8+ CD 28+ and CD40L subsets of vcDC-T cells was increased [(47.6±15.8)% vs (38.2±7.6)%, (52.1±4.9)% vs (44.7±3.2)% ] compared with that of DC-T cells, the ratio of negative regulatory cells (Treg) was decreased [(4.3±0.8)% vs (8.3±1.1)%]; the release of IL-2, IFN-γ and IL-12 was increased [(201.2±17.3) ng/L, (163.4±13.1)ng/L, (303.3±22.6)ng/L vs 221.8±17.6)ng/L, (190.4±11.7)ng/L vs (80.3±8.6)ng/L]. All the differences were statistically significant ( P<0.01). 100 ng CD 3/KIF20A loaded T cells were observed under microscope, which obviously targeted KIF20A + pancreatic cancer PANC1 cells and had a strongest killing power. At the killing cells to targeting cells ratio of 20∶1 with 4-hour coculture, the killing rate of CD 3/KIF20A-vcDC-T cells on PANC1 cells was (88.6±2.6)%, which was significantly higher than (68.4±3.4)% and (39.2±2.1)% in the CD3/KIF20A-DC-T group and (39.2±2.1)% in the DC-T group, increasing by 20% and at lease 45%, respectively. Conclusions:DC-T cells loaded with CD 3/KIF20A antibody can significantly increase the killing rate of KIF20A positive pancreatic cancer PANC1 cells, and vitamin C intervention can further enhance the killing ability of antibody loaded T cells.
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ObjectiveTo investigate the effect of the immunotherapy of CIK cell, LAK cell and PBLS cell mediated by anti-EGFR/anti-CD3 bispecific antibody (BsAb) respectively on the mice borne human gastric cancer and provide experimental evidence for therapeutic strategy in treating gastric cancer. Methods The mAbs of anti-CD3 and anti-EGFR were cross-linked to prepare the BsAb by chemical synthesis. The experimental therapy on the mice borne SGC7901 human gastric cancer was performed,and then the comparisons of the curative activity among the CIK group, LAK group and PBLS group were conducted in vivo. ResultsThe mean tumor reduction rate of the administration of CIK cells directed by anti-EGFR/anti-CD3 BsAb was(64.9±7.7)％ and higher than those of LAK cells or PBLS targeted by anti-EGFR/anti-CD3 BsAb [(43.5±8.2) ％ and (39.7±6.5) ％] (P ＜ 0.05).The mean tumor weight of the administration of CIK cells directed by anti-EGFR/anti-CD3 BsAb was (473.9±37.7) mg at the end of therapy and was lower than those of LAK cells or PBLS targeted by anti-EGFR/anti-CD3 BsAb [(764.6±88.3) mg and (829.1±104.4) mg](P ＜ 0.05). ConclusionThe CIK cell mediated by anti-EGFR/anti-CD3 BsAb could have better curative effect than other effector cells on gastric cancer in vivo.
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Objective: : To observe whether cytokines rIL 2,TNF ?,I FN ? and anti CD3/anti glioma bispecific antibody(BsAb) can work coordinately, and to investigate how to further enhance cytotoxicity of T lymphocyte against human glioma cells by BsAb. Methods: There were 12 groups,contr ast method were used to analyze the effect of cytokines rIL 2,TNF ?,IFN ? to cytoxicity directed by BsAb by single and combined experiments. Cytotoxicity was assayed by standard 18 h 3H TdR incorporation release. Resul ts: rIL 2,TNF ?,IFN ? and BsAb could cooperatively enhance the cy totoxicity of effect cells( P
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Objective: To study bidirectional binding ability and immunoactivity of anti-CD3/anti-glioma bispecific antibodies(BsAb) , and to study its effect on T lymphocytes cells. Methods: Elution from standardized gel column and immnuohistochemical method were used to testify the relative molecular mass of the compound. ELISA method was used to detect its bidirectional immunoactivity and potential T lymphocytes' cytotoxicity. Phenotype and shape of T lymphocytes were also observed. Results: The relative molecular mass of the compound was 110 000, and it combined with both T lymphocytes and glioma cells.Immunoactivity assay showed the compound had good bidirectional immunoactivity. It also enhanced T lympocytes anti-tumor activity. Immunoactivity of BsAb combining with T lymphocytes was 1∶32 000, and combining with glioma cells was 1∶8 000;In phenotypes, CD3 + cells were the major one when cultivated with BsAb/IL-2, CD8 + cells increased gradually with cultivation time. Conclusion: These compounds are bispecific antibodies with bidirectional combining activity to T lymphocytes and glioma cells, they also have bidirectional immunoactivity and can activate T lymphocytes