title: Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far.
  
  
  
  In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone.
  
  
  
  This case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation.
  
  
  
  ClinicalTrials.gov NCT01869166 and NCT02541370 .
authors.affiliation: Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Kai-Chao
authors.initials: KC
authors.lastname: Feng
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Ye-Lei
authors.initials: YL
authors.lastname: Guo
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Han-Ren
authors.initials: HR
authors.lastname: Dai
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Lv
authors.affiliation: Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Qing-Ming
authors.initials: QM
authors.lastname: Yang
authors.affiliation: Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China. hanwdrsw69@yahoo.com.|Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China. hanwdrsw69@yahoo.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Han
mesh_terms: D000071916:AC133 Antigen / Q000008:administration & dosage / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000628:therapy*; D018281:Cholangiocarcinoma / Q000628:therapy*; D066246:ErbB Receptors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods; D013601:T-Lymphocytes; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: CART cocktail immunotherapy; CD133; Cholangiocarcinoma; EGFR