Strategies for successful vaccination against hepatocellular carcinoma.
Current therapies against hepatocellular carcinoma (HCC) are not curative in the majority of patients. In the past, immunotherapy approaches aimed to non-specifically stimulate immune response were quite ineffective. New treatments based on stimulation of specific anti-tumor immune response are currently proposed and appear more promising. Tumor-specific antigens identified in HCC demonstrated immunogenicity both in preclinical and clinical trials. Effectiveness in animal studies raised interest in the clinical applicability of non-specific adoptive immunotherapy that prevented disease recurrence after tumor resection. Dendritic cell (DC)-based tumor vaccines achieved encouraging results, and cellular vaccines based on DCs have already entered clinical trials. Preventive and therapeutic DNA vaccination have been proposed, all based on tumor-associated antigens (TAAs), either modified or not, an example being alpha-fetoprotein (AFP). The concomitant expression of co-stimulatory molecules and cytokines was used to increase tumor immunogenicity. Syngeneic or nude mice models indicated that immunotherapy for HCC could stimulate an anti-tumor T-cell response leading to clinical benefit devoid of significant toxicity. The use of DNA-based vaccination raises exciting possibilities in preventing HCC in high-risk individuals such as those with cirrhosis. Novel immunotherapy strategies may contribute in the future to prevention and treatment of HCC.
Rinaldi
M
M
Iurescia
S
S
Fioretti
D
D
Ponzetto
A
A
Carloni
G
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D016219:Immunotherapy, Adoptive; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016896:Treatment Outcome; D019444:Vaccines, DNA
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018925:Chemokines; D016207:Cytokines; D019444:Vaccines, DNA