The goal of this clinical trial is to study the feasibility and efficacy of anti-CD22:TCRz:4-1BB chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating recurrent patients with refractory or resistant lymphoma to anti-CD19:TCRz:CD28 CAR-T cells. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the recession of evaluable lesions, the persistence and efficacy of CAR-T cells are still restricted by the "target" selection. Previous clinical studies largely utilized CD19 for the in vivo targeting of CAR-T cells, which preferentially become refractory or resistant due to the heterogeneity of lymphoma. This clinical investigation is to test a hypothesis whether anti-CD22 CAR-T cells work more effective in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells.
Primary Objectives 1. To determine the safety of CD22.CAR-T cells in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells 2. To determine in vivo dynamics and persistency of CD22.CAR-T cells. Secondary Objectives 1. To determine the feasibility of CD22.CAR-T cells in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells 2. To determine in vivo dynamics and persistency of CD22.CAR-T cells. 3. To assess the intratumoral infiltration of CD22.CAR-T cells. 4. To correlate the subsets and differentiation of CD22.CAR-T cells to observed anti-tumor efficacy
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Department of Oncology, Xinqiao Hospital
Chongqing, Chongqing Municipality, China
RECRUITINGSafety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Time frame: 4 Weeks
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Time frame: 8 Weeks
Duration of CAR-positive T cells in circulation
Time frame: 6 months
Total number of CAR-positive T cells infiltrated into lymphoma tissue
Time frame: 6 months
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