Contributions
Abstract: EP742
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
In the past few years, Chimeric Antigen Recepter T-cell(CAR-T) immunotherapy played as a superstar treating acute lymphocytic leukemia(ALL). CD19 CAR-T has been widely used on refractory or relapse B-ALL patients with exciting outcomes. CD7 has been pointed out as a potential target for treating T-ALL. According to our unpublished data, the manifestation of patients treated with CD7 CAR-T is different from the patients treated with CD19 CAR-T. In this experiment, we tried to figure out the difference between CD19 CAR-T and CD7 CAR-T in serum cytokine levels and peak time for guiding clinical practice.
Aims
To figure out the differences in serum cytokine level and peak time between samples of CD19 CAR-T treated and CD7 CAR-T treated.
Methods
peripheral blood sample were collected from 86 patients treated with CD19 CAR-T and 10 patients treated with CD7 CAR-T. According to CRS severity grading, 79/86 were classified as CD19 CRS low grades (0-2 grade), 7/86 as CD19 CRS high grades (higher than 3 grade), and 7/10 as CD7 CRS low grades, 3/10 as CD7 CRS high grades. 24 cytokines QBplex microbeads kits for cytokine monitoring were bought from Beijing Quantobio Company. Cytokine samples were analyzed by flow cytometry on day0, 4, 7, 11, 15, 20, and 30 after CAR-T infusion. ScFV positive CAR-T cells and T cells percentage and counts were detected at the same time by flow cytometry.
Results
Two group had similar ScFV positive CAR-T cells with median peak percentage 53% in CD7 CAR-T and 57% in CD19 CAR-T group, and median counts in peak time were 1.55X10e8/L in CD7 group and 2X10e8/L in CD19 group. Firstly, most cytokines from patients treated with CD7 CAR-T were obviously higher than those from the patients with CD19 CAR-T treatment in CRS low grades. Secondly, in CRS high grades, most of the cytokines were secreted and reached a peak value in both of CD7 and CD19 CAR-T group. On the other hand, the peak time was earlier in CD19 group than CD7 group. Many main cytokines reached peak value between day7 and day 10 in CD19 group, and in CD7 group were between day 11 and day 15, even on day 20 in some cases. Besides, in CRS low grades, the expression levels were fairly low in CD19 CAR-T group, but those were much higher in CD7 group. In most cases, there were clinical CRS manifestations corresponding to cytokine levels in CD7 group and none or mild symptoms in CD19 group. In other words, most patients treated with CD7 CAR-T had higher cytokine levels and showed more intense symptoms than patients with CD19 CAR-T, even with CRS low grade. Meanwhile, in many cases, side-effects showed up later in CD7 CAR-T group than that in CD19 CAR-T group which corresponding to later peak time in CD7 group.
Conclusion
Most cytokine levels were higher in CD7 CAR-T group than CD19 CAR-T cases in CRS low grade, and reached peak time later in CD7 group. Clinical symptoms showed corresponding to cytokine levels in most cases. Although different technique and activated cell number might result these, serum cytokines played an important role in CAR-T therapy and study.
Keyword(s):
Abstract: EP742
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
In the past few years, Chimeric Antigen Recepter T-cell(CAR-T) immunotherapy played as a superstar treating acute lymphocytic leukemia(ALL). CD19 CAR-T has been widely used on refractory or relapse B-ALL patients with exciting outcomes. CD7 has been pointed out as a potential target for treating T-ALL. According to our unpublished data, the manifestation of patients treated with CD7 CAR-T is different from the patients treated with CD19 CAR-T. In this experiment, we tried to figure out the difference between CD19 CAR-T and CD7 CAR-T in serum cytokine levels and peak time for guiding clinical practice.
Aims
To figure out the differences in serum cytokine level and peak time between samples of CD19 CAR-T treated and CD7 CAR-T treated.
Methods
peripheral blood sample were collected from 86 patients treated with CD19 CAR-T and 10 patients treated with CD7 CAR-T. According to CRS severity grading, 79/86 were classified as CD19 CRS low grades (0-2 grade), 7/86 as CD19 CRS high grades (higher than 3 grade), and 7/10 as CD7 CRS low grades, 3/10 as CD7 CRS high grades. 24 cytokines QBplex microbeads kits for cytokine monitoring were bought from Beijing Quantobio Company. Cytokine samples were analyzed by flow cytometry on day0, 4, 7, 11, 15, 20, and 30 after CAR-T infusion. ScFV positive CAR-T cells and T cells percentage and counts were detected at the same time by flow cytometry.
Results
Two group had similar ScFV positive CAR-T cells with median peak percentage 53% in CD7 CAR-T and 57% in CD19 CAR-T group, and median counts in peak time were 1.55X10e8/L in CD7 group and 2X10e8/L in CD19 group. Firstly, most cytokines from patients treated with CD7 CAR-T were obviously higher than those from the patients with CD19 CAR-T treatment in CRS low grades. Secondly, in CRS high grades, most of the cytokines were secreted and reached a peak value in both of CD7 and CD19 CAR-T group. On the other hand, the peak time was earlier in CD19 group than CD7 group. Many main cytokines reached peak value between day7 and day 10 in CD19 group, and in CD7 group were between day 11 and day 15, even on day 20 in some cases. Besides, in CRS low grades, the expression levels were fairly low in CD19 CAR-T group, but those were much higher in CD7 group. In most cases, there were clinical CRS manifestations corresponding to cytokine levels in CD7 group and none or mild symptoms in CD19 group. In other words, most patients treated with CD7 CAR-T had higher cytokine levels and showed more intense symptoms than patients with CD19 CAR-T, even with CRS low grade. Meanwhile, in many cases, side-effects showed up later in CD7 CAR-T group than that in CD19 CAR-T group which corresponding to later peak time in CD7 group.
Conclusion
Most cytokine levels were higher in CD7 CAR-T group than CD19 CAR-T cases in CRS low grade, and reached peak time later in CD7 group. Clinical symptoms showed corresponding to cytokine levels in most cases. Although different technique and activated cell number might result these, serum cytokines played an important role in CAR-T therapy and study.
Keyword(s):