Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers.
10.1007/s13238-017-0440-4
- Author:
Kaichao FENG
1
;
Yang LIU
2
;
Yelei GUO
3
;
Jingdan QIU
1
;
Zhiqiang WU
3
;
Hanren DAI
3
;
Qingming YANG
1
;
Yao WANG
3
;
Weidong HAN
4
Author Information
1. Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, 100853, China.
2. Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
3. Department of Molecular & Immunology, Chinese PLA General Hospital, Beijing, 100853, China.
4. Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, 100853, China. hanwdrsw69@yahoo.com.
- Publication Type:Journal Article
- Keywords:
CART;
HER2;
biliary tract cancers;
clinical trial;
pancreatic cancers
- MeSH:
Aged;
Biliary Tract Neoplasms;
immunology;
therapy;
Female;
Humans;
Immunotherapy, Adoptive;
Male;
Middle Aged;
Pancreatic Neoplasms;
immunology;
therapy;
Receptor, ErbB-2;
immunology;
Receptors, Chimeric Antigen;
immunology;
T-Lymphocytes;
immunology
- From:
Protein & Cell
2018;9(10):838-847
- CountryChina
- Language:English
-
Abstract:
This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100-200 mg/m) and cyclophosphamide (15-35 mg/kg). CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART-HER2 cell infusion (median CAR T cell 2.1 × 10/kg). The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgia/arthralgia, and lymphopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase (>9 ULN), adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastrointestinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2 delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months (range, 1.5-8.3 months). Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encouraging signals of clinical activity.
