Patients with refractory and/or recurrent solid tumor have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat these diseases using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (4SCAR fused with an inducible apoptotic caspase 9 domain) targeting GD2 (4SCAR-GD2). The 4SCAR-GD2-modified T cells can recognize and kill tumor cells through the recognition of GD2, a surface protein expressed at high levels on many types of tumors but not on normal tissues. This study will evaluate the side effects and effective doses of 4SCAR-GD2 T cells in treating refractory and/or recurrent tumors.
Background: Patients with refractory and/or recurrent solid tumors have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a 4th generation GD2-specific chimeric antigen receptor (4SCAR-GD2). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, GD2, which is expressed at high levels on tumor cells but not at significant levels on normal tissues. This study will evaluate the side effects and the best dose of a novel 4th generation anti-GD2 CAR T cells to refractory and/or recurrent solid tumors. Design: Participants will be screened through physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow aspirates may be performed. Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-GD2 gene. On Day -5 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-GD2 lentiviral transduction. The total culture time is approximately 5-7 days. Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accept the modified CAR T cells.The preparative regimen will be based on patient immune condition and consistent with standard chemotherapy conditioning regimen.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
GD2-specific 4th Generation CART
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China
RECRUITINGNumber of patients with adverse events.
Determine the toxicity profile the 4SCAR-GD2-modified T cells with Common Toxicity Criteria for Adverse Effects version 4.0
Time frame: 3 year
Anti-tumor effects
Disease status is defined by the biochemical markers and image scan to get the outcomes such as Complete response/remission (CR) , Very good partial response/remission (VGPR) , etc
Time frame: 3 year
The expansion and persistence of anti-GD2 CAR T cells
The investigators will monitor the expansion and functional persistence of 4SCAR-GD2 T cells in the peripheral blood of patients and the correlation with antitumor effects
Time frame: 3 year
Immune responses after anti-GD2 infusions
assessment of lymphocyte phenotypes and anti-tumor activity
Time frame: 1 year
Immune responses after anti-GD2 infusions
assessment of cytokine profile
Time frame: 1 year
Survival time of the patients
Evaluate the survival time of the patients treated with the 4SCAR-GD2 T cells, including progression free survival (PFS) and overall survival (OS)
Time frame: 3 year
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