Strategies for Successful Vaccination against Hepatocellular Carcinoma

Abstract

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.

Hepatocellular Carcinoma

“…In addition, significant variation in the heterogeneity of the molecular and cellular makeup of HCC due to multiple etiological factors has posed significant problems. Nevertheless, efforts are underway to develop locally applied oncolytic viral agents as well as more DNA, peptide, viral, and dendritic cell-based vaccines for HCC (Rinaldi et al 2009;Zhang et al 2009;Pardee and Butterfield 2012). In a recent study, DC-mediated CTLs were effectively targeted to CSCs in HCC .…”

“…Integration of molecular biomarkers identified from various different studies with these drug targets would allow us to identify potential candidates for drug response. A final area of therapy is immunotherapy; and there are ongoing efforts to develop locally applied oncolytic viral agents for tumor destruction as well as more conventional efforts towards vaccination against tumors (Rinaldi et al 2009;Tian et al 2009;Zhang et al 2009). …”

DNA Vaccines: Developing New Strategies against Cancer

“…In preclinical studies, mice were successfully DNA-based immunized [147]. In a prime-boost approach, coadministration of plasmids DNA encoding murine alpha fetoprotein (AFP) and murine GM-CSF was followed by boosting with an AFP-expressing nonreplicating adenoviral vector [60] leading to tumor protective immunity.…”

Nano-bilosomes as potential vaccine delivery system for effective combined oral immunization against tetanus and hepatitis B

“…We are also exploring the possibility of improved delivery of probiotic bacteria using a similar formulations. DNA vaccine platform has produced exciting results in a wide array of applications, from prophylactic vaccine strategies to potential therapeutics targeting cancers and infectious disease (Fioretti et al, 2010;Rinaldi et al, 2009;Rinaldi et al, 2006;Fazio et al, 2004).…”