Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for 35% of lymphoma. Chimeric antigen receptor T cell (CAR-T) therapy is a new method to treat DLBCL. KTE-C19, published in the New England Medical Journal in December 2017, was used to treat relapsed and refractory B-cell lymphoma. One year of treatment for 111 patients, the total response rate was 82%, and the complete remission rate was 54%. However, a large number of clinical studies have shown that about 20% of patients with B-ALL and 50% of patients with B-NHL cannot achieve complete remission (CR) after CD19-CAR-T treatment. Targeting tumor microenvironment is an important new method to overcome the drug resistance of CAR-T cells. In this study, IL-7 and CCL19 were connected on the basis of traditional second generation CD19 CAR-T cells to construct novel fourth generation CAR-T cells, which can promote the infiltration, accumulation and survival of CAR-T cells in lymphoma tissue, and further enhance the anti-tumor effect of traditional CAR-T cells. At the same time, combined with four generations of CAR-T cells and PD1 monoclonal antibody, PD1 / PDL1 signal pathway was blocked, anti-tumor effect of CAR-T was improved, and immune response and long-term remission rate of DLBCL were improved.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Three different doses of CD19-7×19 CAR-T (1×106/kg、2×106/kg、3×106/kg) plus 200mg Tislelizumab every 3 weeks for 6 times
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
Objective response rate
Objective response rate of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb
Time frame: 3 months
progression-free survival
progression-free survival of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb
Time frame: 2 years
overall survival
overall survival of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb
Time frame: 2 years
Duration of Overall Response
Duration of Overall Response of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb
Time frame: 2 years
Relapse rate
Relapse rate of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb
Time frame: 2 years
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