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Recently, the team of the Department of Hematology at the Second Affiliated Hospital of Zhejiang University School of Medicine published a paper in the Journal of Hematology & Oncology, demonstrating the use of the new CD19-PD-1/CD28-CAR-T technology for the rescue treatment of CD19-CAR-T After treatment fails, patients with diffuse large B-cell lymphoma (DLBCL) can achieve good results.
Chimeric antigen receptor T cell (CAR-T) is a type of T cell modified by genetic engineering technology, which can directly recognize the antigen on the surface of tumor cells, thereby specifically killing tumor cells.
CD19-CAR-T cell therapy improves the prognosis of patients with relapsed and refractory (R/R) DLBCL.
About 40% of patients can get long-term remission, but nearly half of the patients still end up after receiving CAR-T treatment.
Will relapse and progress to be refractory to death.
Spiegel et al.
reported the follow-up results of patients with R/R large B-cell lymphoma after receiving CD19-CAR-T.
The median overall survival (OS) was 180 days (95% CI: 105-242).
After CAR-T treatment The prognosis of relapsed patients is extremely poor, and follow-up treatment for these patients has become a difficult point.
From January 2018 to August 2019, the Second Affiliated Hospital of Zhejiang University School of Medicine enrolled 6 patients with R/R DLBCL who failed after receiving CD19-CAR-T treatment.
The baseline status of the patients is shown in Table 1.
Among the 6 patients There are 3 cases of CD19-CAR-T treatment ineffective, 2 cases have achieved partial remission (PR), remission periods were 3 months and 4 months, respectively, and 1 case sustained remission for 30 months before recurrence.
Table 1: Status of the 6 patients enrolled in the 6 patients.
All the 6 patients successfully used autologous peripheral blood mononuclear cells or cryopreserved autologous peripheral blood mononuclear cells to prepare CD19-PD-1/CD28-CAR-T cells.-5 days to -3 days to receive a pretreatment regimen containing cyclophosphamide 500mg/m2 and fludarabine 30mg/m2, and intravenous infusion of CD19-PD-1/CD28-CAR-T as a rescue treatment.
The number of CAR-T cells ranged from 0.
32×106 to 4×106/kg.
3 patients (3/6) developed grade 1 cytokine release syndrome (CRS), 2 patients (2/6) developed grade 2 CRS, patients 4 and 6 developed both grade 2 CRS and grade 3 immune effector cells Related Neurotoxicity Syndrome (ICANS).
Changes in serum cytokine levels were detected in all patients within one month after the second CAR-T treatment.
Increased IL-6, IL-4, IL-2 and TNFα in patient 1; IL-6, IL-4, IL-2, IL-17A and IFNγ in patient 4 who had undergone grade 2 CRS and grade 3 ICANS The level was elevated, but no similar situation was observed in patient No.
6.
4 cases of CRS were completely remitted (CR) after supportive treatment, and 2 cases of CRS and ICANS were completely remitted after supportive treatment, tocilizumab and glucocorticoid treatment.
Table 2: Analysis of adverse events as of October 1, 2020, with a median follow-up of 14 months.
According to the efficacy evaluation criteria of the International Lymphoma Working Group, FDG-PET-CT was used to evaluate the efficacy 3 months after receiving the second CAR-T infusion.
Three patients (3/6) achieved CR, one patient had stable disease (SD), and two patients (2/6) died of disease progression within 60 days.
Of the 3 patients who achieved CR, 2 were still in CR at the last follow-up, but the other patient relapsed within 8 months after treatment and died 12 months later.
The CAR-T cells in the blood of patients were monitored by qPCR technology, which reached a peak within 2 weeks after infusion.
However, there was no significant difference in the number of CAR-positive cells in the peak blood of patients who responded to treatment and those who did not.
Significantly, the number of CAR+ cells in patient No.
3 dropped rapidly after reaching the peak, but increased significantly on the 540th day after treatment.
This patient achieved long-term remission. Figure 1: Patient efficacy evaluation studies have confirmed that for patients whose first CD19-CAR-T is ineffective or relapsed, the new CD19-PD-1/CD28-CAR-T secondary CAR-T can be used as an effective rescue treatment measure .
Reference source: Yun Liang, Hui Liu, Zheming Lu, et al.
CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies.
J Hematol Oncol .
2021 Feb 16;14(1):26.
doi: 10.
1186/s13045-021-01044-y.
Stamp "read the original text", we make progress together
Chimeric antigen receptor T cell (CAR-T) is a type of T cell modified by genetic engineering technology, which can directly recognize the antigen on the surface of tumor cells, thereby specifically killing tumor cells.
CD19-CAR-T cell therapy improves the prognosis of patients with relapsed and refractory (R/R) DLBCL.
About 40% of patients can get long-term remission, but nearly half of the patients still end up after receiving CAR-T treatment.
Will relapse and progress to be refractory to death.
Spiegel et al.
reported the follow-up results of patients with R/R large B-cell lymphoma after receiving CD19-CAR-T.
The median overall survival (OS) was 180 days (95% CI: 105-242).
After CAR-T treatment The prognosis of relapsed patients is extremely poor, and follow-up treatment for these patients has become a difficult point.
From January 2018 to August 2019, the Second Affiliated Hospital of Zhejiang University School of Medicine enrolled 6 patients with R/R DLBCL who failed after receiving CD19-CAR-T treatment.
The baseline status of the patients is shown in Table 1.
Among the 6 patients There are 3 cases of CD19-CAR-T treatment ineffective, 2 cases have achieved partial remission (PR), remission periods were 3 months and 4 months, respectively, and 1 case sustained remission for 30 months before recurrence.
Table 1: Status of the 6 patients enrolled in the 6 patients.
All the 6 patients successfully used autologous peripheral blood mononuclear cells or cryopreserved autologous peripheral blood mononuclear cells to prepare CD19-PD-1/CD28-CAR-T cells.-5 days to -3 days to receive a pretreatment regimen containing cyclophosphamide 500mg/m2 and fludarabine 30mg/m2, and intravenous infusion of CD19-PD-1/CD28-CAR-T as a rescue treatment.
The number of CAR-T cells ranged from 0.
32×106 to 4×106/kg.
3 patients (3/6) developed grade 1 cytokine release syndrome (CRS), 2 patients (2/6) developed grade 2 CRS, patients 4 and 6 developed both grade 2 CRS and grade 3 immune effector cells Related Neurotoxicity Syndrome (ICANS).
Changes in serum cytokine levels were detected in all patients within one month after the second CAR-T treatment.
Increased IL-6, IL-4, IL-2 and TNFα in patient 1; IL-6, IL-4, IL-2, IL-17A and IFNγ in patient 4 who had undergone grade 2 CRS and grade 3 ICANS The level was elevated, but no similar situation was observed in patient No.
6.
4 cases of CRS were completely remitted (CR) after supportive treatment, and 2 cases of CRS and ICANS were completely remitted after supportive treatment, tocilizumab and glucocorticoid treatment.
Table 2: Analysis of adverse events as of October 1, 2020, with a median follow-up of 14 months.
According to the efficacy evaluation criteria of the International Lymphoma Working Group, FDG-PET-CT was used to evaluate the efficacy 3 months after receiving the second CAR-T infusion.
Three patients (3/6) achieved CR, one patient had stable disease (SD), and two patients (2/6) died of disease progression within 60 days.
Of the 3 patients who achieved CR, 2 were still in CR at the last follow-up, but the other patient relapsed within 8 months after treatment and died 12 months later.
The CAR-T cells in the blood of patients were monitored by qPCR technology, which reached a peak within 2 weeks after infusion.
However, there was no significant difference in the number of CAR-positive cells in the peak blood of patients who responded to treatment and those who did not.
Significantly, the number of CAR+ cells in patient No.
3 dropped rapidly after reaching the peak, but increased significantly on the 540th day after treatment.
This patient achieved long-term remission. Figure 1: Patient efficacy evaluation studies have confirmed that for patients whose first CD19-CAR-T is ineffective or relapsed, the new CD19-PD-1/CD28-CAR-T secondary CAR-T can be used as an effective rescue treatment measure .
Reference source: Yun Liang, Hui Liu, Zheming Lu, et al.
CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies.
J Hematol Oncol .
2021 Feb 16;14(1):26.
doi: 10.
1186/s13045-021-01044-y.
Stamp "read the original text", we make progress together
