Weidong Han
Professor Chinese PLA General Hospital China
Title: Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with sorafenib refractory hepatocellular carcinoma (HCC) and other solid tumors
Biography
Biography: Weidong Han
Abstract
CD133 is well documented to be expressed by tumor initiating cells and epithelial progenitor cells which were proposed to have predominant roles for tumor recurrence and pre-metastatic niche formation, respectively. Thus, targeting CD133 might help eradicate the primary tumors and even prevent tumor metastasis. Herein, CD133-directed chimeric antigen receptor modified T-cells (CART-133) were prepared and their specific targeting activity was verified. Results from hematopoietic colony forming assays suggested that CART-133 cells may pose no irreversible myelosuppression. Eight patients with advanced and sorafenib refractory HCC were enrolled on phase-I trial. They were assigned into 3 dose-escalated cohorts and were treated by repeated CART-133 monotherapy once 4-8 weeks. All patients had tolerable febrile syndromes during cell infusions. Rapid ascites growth occurred in 1 patient during infusion and was resolved by the use of diuretic. One patient developed transiently drastic decline of hemoglobin and platelets and Grade 3 direct hyperbilirubinemia within 2 weeks. Reverse correlation between CD133+ cells in PB and CAR copy number in cohort 2 and 3 revealed an effective biological activity of CART-133 and its rational expansion dose. 1 of 3 cases in cohort 1 aggressively progressed after cell therapy and became stable after transferred to cohort 2. Seven cases maintained stable disease so far, however, 2 patients died of upper gastrointestinal massive hemorrhage >9 weeks after infusion. Based on these, 7 additional patients with other metastatic solid tumors were enrolled into phase-II trial using the expansion dose, the response of which is under evaluation.