机构:[1]College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China[2]Jinan University Affiliated Guangdong 999 Brain Hospital, Guangzhou, People’s Republic of China[3]Beijing Tricision Biotherapeutics Corporation, Beijing, People’s Republic of China[4]Guangzhou Trinomab Biotechnology Corporation, Guangzhou, People’s Republic of China[5]First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China[6]MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China[7]The Cancer Center, Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China四川省人民医院[8]Department of Immunology, Duke University Medical Center, Box 3010, Durham, NC 27710, USA
Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4(+) and/or CD8(+) T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4(+) and CD8(+) T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.
基金:
The study was supported by Beijing Tricision Biotherapeutics
Inc and Guangzhou Trinomab Inc. The project is also in part supported
by the Guangdong Innovative and Entrepreneurial Research
Team Program (No 2013Y113), Zhuhai Innovative and Entrepreneurial
Research Team Program (No ZH01110405160015PWC), and National
Basic Research Program of China (No 2015CB553706) to HX Liao at
Jinan University.
第一作者机构:[1]College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China[2]Jinan University Affiliated Guangdong 999 Brain Hospital, Guangzhou, People’s Republic of China