4SCAR-CD44v6 T Cell Therapy Targeting Cancer

CD44 variant domain 6 (CD44v6) which belongs to CD44 family has been implicated in tumorigenesis, tumor cell invasion and metastasis. The expression of CD44v6 was reported for the majority of squamous cell carcinomas, a proportion of adenocarcinomas of differing origin, a proportion of melanoma and lymphoma. This expression pattern has made CD44v6 an attractive target for the therapy of various types of CD44v6 positive cancers.

The T cells from patients or transplantation donors will be genetically modified with lentiviral CAR vector to recognize specific molecules - CD44v6 expressed on the surface of the cancer cells. The engineered T cells will be applied to patients through intravenous delivery.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of CD44v6 CAR-T cell therapy in multiple cancers including - but not limited to - stomach cancer, breast cancer, prostate cancer, multiple myeloma and lymphoma which are CD44v6 positive. Another goal of the study is to learn more about the function of the 4SCAR-CD44v6 T cells and their persistency in the patients.

Inclusion criteria

• Age older than 6 months.
• Confirmed expression of CD44v6 in tumor specimens by immuno-histochemical staining or flow cytometry.
• Karnofsky performance status (KPS) score is higher than 70 and life expectancy > 3 months.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
• Hgb≥80g/L.
• No cell separation contraindications.
• Abilities to understand and the willingness to provide written informed consent.

Exclusion criteria

• Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
• Active bacterial, fungal or viral infection not controlled by adequate treatment.
• Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Pregnant or nursing women may not participate.
• Use of glucocorticoid for systemic therapy within one week prior to entering the trial.
• Receive treatment related to CD44v6 targeted therapy.
• Patients, in the opinion of investigators, may not be able to comply with the study.