Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Humanized CAR-T Therapy for Treatment of Recurrent or Refractory B Cell Malignancy by Targeting CD19

The present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a humanized scFv. All participants will receive autologous chimeric antigen receptor engineered T cells.

CD19 has been extensively evaluated as a therapeutic target for recurrent or refractory B cell malignancy by chimeric antigen receptor T cell therapy, the single chain antibody sequence (scFv) against CD19 derived from a mouse hybridoma was widely employed. However, the immunogenicity of the mouse scFv sequence might be one of the reasons that CAR-T cells cannot persist in vivo for long. In present study investigators replace the mouse-derived scFv with a a humanized one and evaluate its safety and efficacy.

Inclusion Criteria:

• Age≥3 at the time of consent
• Survival time>12 weeks
• B cell hematological malignancies by pathological examination
• Chemotherapy failure or recurrent B cell malignancy
• Creatinine< 2.5mg/dl
• Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level
• Karnofsky Performance Status>50% at the time of screening
• Bilirubin<2.0mg/dl
• Adequate pulmonary, renal, hepatic, and cardiac function
• Fail in autologous or allogenic haemopoietic stem cell transplantation
• Free of leukocytes removal contraindications

Exclusion Criteria:

• Pregnant or nursing women
• Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
• Previous treatment with any gene therapy product
• Abnormal vital signs
• Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2
• General infection or local severe infection, or other infection that is not controlled
• Dysfunction in lung, heart, kidney and brain.
• Severe autoimmune diseases
• other symptoms that are not applicable for CAR-T