Phase-I/IIa trial of chimeric antigen receptor modified T-cells a | 32475
Immunotherapy: Open Access

Immunotherapy: Open Access
Open Access

ISSN: 2471-9552

+44 1223 790975

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

International Conference on Tumor & Cancer Immunology and Immunotherapy

July 28-30, 2016 Melbourne, Australia

Weidong Han

PLA General Hospital, China

Scientific Tracks Abstracts: Immunother Open Acc

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.

Biography :

Weidong Han has obtained his PhD degree in Clinical Hematology from Chinese PLA Postgraduate Medical School in 2001 and worked in Department of Molecule & Immunology of Chinese PLA General Hospital. In 2003, he did Postdoctoral work at the University College London. In 2006, he was promoted to Professor of Molecular and Cellular Biology. Presently, he is the Director of Department of Molecular and Cellular Biology, Director of Clinical Translational Ward, the General Hospital of PLA. Since 2001, he focused on mechanism research involved in cancer treatment resistance and clinical translation of cell therapy. He has published over 80 articles.