The purpose of this study is to assess the feasibility, safety and efficacy of multiple 4th generation CAR-T cells targeting Her2, GD2, and CD44v6 surface antigen in breast cancer. Another goal of the study is to learn more about the activities of the multi-CAR T cells and their persistency in the patients.
Breast cancer is one of the most frequent cancer types in women. The average risk of a woman in the United States developing breast cancer in her life is about 13%. That means that there is a 1 in 8 chance she will develop breast cancer. Human epidermal growth factor receptor-2 (HER2) is one of the more well-researched genes in breast cancer so far. It has been reported that HER2 gene is overexpressed in 20% to 30% of breast cancer patients. HER2 is an important target for tumor gene therapy. In 2003, scientists confirmed the existence of breast cancer stem cells. In 2012, ganglioside GD2 was confirmed as an emerging marker of breast cancer stem cells. Targeting therapies for GD2 may help improve the survival rate and cure rate of breast cancer patients. Invasion and metastasis of tumor cells is the main cause of cancer death. CD44v6 is an adhesion molecule on the cell surface, which not only promotes epithelial-mesenchymal transition, degradation and remodeling of extracellular matrix, but also participates in organ-specific metastasis of tumor cells. Studies have shown that overexpression of CD44v6 is an important factor for the invasion and metastasis of breast cancer, and is closely related to the tumor size of the breast cancer, tumor staging, and lymph node metastasis. Therefore, CD44v6 may be an important target for the treatment of breast cancer. Using Her2-, GD2- and CD44v6-specific CAR-T cells may effectively improve the immunotherapy treatment, prevent tumor cells from escaping treatment, and achieve the effect of long-term disease relief.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Infusion of 4SCAR-GD2, -Her2 and -CD44v6 CAR-T cells
The Seventh Affilliated Hospital, Sun Yat-Sen University
Shenzhen, Guangdong, China
RECRUITINGNumber of patients with adverse events.
Determine the toxicity profile the multi-4SCAR-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 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 CAR-T cells
The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.
Time frame: 3 months
Survival time of the patients
The survival time of the patients treated with the multi-4SCAR T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.
Time frame: 3 year
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