title: Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial.
abstract: Purpose:Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma.Experimental Design:Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).Results:Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 107CAR-positive T cell per kg (SD, 0.25; range, 1.1-2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.Conclusions:CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment.Clin Cancer Res; 23(5); 1156-66. ©2016 AACR.
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Chun-Meng
authors: CM
authors: Wang
authors: Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors: Zhi-Qiang
authors: ZQ
authors: Wu
authors: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors: Yao
authors: Y
authors: Wang
authors: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors: Ye-Lei
authors: YL
authors: Guo
authors: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors: Han-Ren
authors: HR
authors: Dai
authors: Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors: Xiao-Hui
authors: XH
authors: Wang
authors: Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors: Xiang
authors: X
authors: Li
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Ya-Jing
authors: YJ
authors: Zhang
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Wen-Ying
authors: WY
authors: Zhang
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Mei-Xia
authors: MX
authors: Chen
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Kai-Chao
authors: KC
authors: Feng
authors: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China.
authors: Yang
authors: Y
authors: Liu
authors: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China.
authors: Su-Xia
authors: SX
authors: Li
authors: Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China.
authors: Qing-Ming
authors: QM
authors: Yang
authors: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China. hanwdrsw69@yahoo.com.
authors: Wei-Dong
authors: WD
authors: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology; D017730:Ki-1 Antigen / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D011946:Receptors, Antigen / Q000276:immunology / Q000627:therapeutic use; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000627:therapeutic use; D033581:Stem Cell Transplantation
chemical_list: D018796:Immunoconjugates; D017730:Ki-1 Antigen; D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell