Dynamic and specific immune responses against multiple tumor antigens were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy.
Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care.



Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs). DCs were loaded with a peptide pool of multiple HCC-related tumor antigens, and T cells were stimulated by these DCs.



Thirteen patients with HCC received repeated MASCT after tumor resection during which their immune responses were examined. After three courses of MASCT, the frequency of regulatory T cells in the patients' PBMCs significantly decreased (p < 0.001), while the antigen peptide pool-triggered T cell proliferation (p < 0.001) and IFNγ production (p = 0.001) were significantly enhanced. The specific T cell responses against each antigen in the pool were detected in 11 patients, but with individualized distinct patterns. The most immunogenic TAAs for HCC are survivin, CCND1, and RGS5. Moreover, the antigen-specific immune responses observed in tumor-free patients' PBMCs were significantly stronger than that in the patients with recurrence (p = 0.037).



Our study demonstrates that MASCT is well-tolerated by patients with HCC and elicits strong and dynamic immune responses specifically against multiple tumor associated antigens, which may correlate with clinical outcomes.
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.|HRYZ Biotech Co., Shenzhen, China.
Yanyan
Y
Han
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yeting
Y
Wu
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Chou
C
Yang
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jing
J
Huang
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yabing
Y
Guo
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Li
L
Liu
HRYZ Biotech Co., Shenzhen, China.
Ping
P
Chen
HRYZ Biotech Co., Shenzhen, China.
Dongyun
D
Wu
HRYZ Biotech Co., Shenzhen, China.
Junyun
J
Liu
HRYZ Biotech Co., Shenzhen, China.
Jin
J
Li
HRYZ Biotech Co., Shenzhen, China. joe@thyx.com.
Xiangjun
X
Zhou
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. jlhousmu@163.com.
Jinlin
J
Hou
D000951:Antigens, Neoplasm / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D010455:Peptides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D010455:Peptides
Adoptive cell therapy; Dendritic cell vaccine; Immune responses; Liver cancer; Tumor associated antigens