Neoantigen vaccine: An emerging immunotherapy for hepatocellular carcinoma

Abstract

Tumor-specific neoantigens, which are expressed on tumor cells, can induce an effective antitumor cytotoxic T-cell response and mediate tumor regression. Among tumor immunotherapies, neoantigen vaccines are in early human clinical trials and have demonstrated substantial efficiency. Compared with more neoantigens in melanoma, the paucity and inefficient identification of effective neoantigens in hepatocellular carcinoma (HCC) remain enormous challenges in effectively treating this malignancy. In this review, we highlight the current development of HCC neoantigens in its generation, screening, and identification. We also discuss the possibility that there are more effective neoantigens in hepatitis B virus (HBV)-related HCC than in non-HBV-related HCC. In addition, since HCC is an immunosuppressive tumor, strategies that reverse immunosuppression and enhance the immune response should be considered for the practical exploitation of HCC neoantigens. In summary, this review offers some strategies to solve existing problems in HCC neoantigen research and provide further insights for immunotherapy.

Therapeutic Vaccines against Hepatocellular Carcinoma in the Immune Checkpoint Inhibitor Era: Time for Neoantigens?

“…Nevertheless, the SNVs present in these genes are rather unique among patients [127], even if it seems that there is a predominance of (C > T), (C > A), (T > C), and (T > G) substitutions [125,128]. Depending on the etiology of the HCC, along with other patient-intrinsic factors, the set of mutated genes can change too (mutational signature), so this is an important feature to consider for improving the identification pipeline and the selection of potential neoAgs for vaccination [125,129].…”

“…Despite the high immunogenicity and specificity of neoAgs, vaccines based on these antigens may behave similarly. Therefore, future strategies should consider the combination of vaccines with immune-stimulating agents and blockade of immune checkpoints to reverse the immunosuppressive environment [129]. A recent vaccination study with personalized neoAgs in 10 HCC patients has demonstrated vaccine safety and immunogenicity, but the low patient number does not allow us to reach solid conclusions on clinical activity [126].…”

Tissue Pathogens and Cancers: A Review of Commonly Seen Manifestations in Histo- and Cytopathology

“…Immunotherapy with agents such as nivolumab and pembrolizumab is also quickly gaining recognition as showing promising results in HCC therapy [90,91]. The use of neoantigen vaccine is emerging as a potential immunotherapy in HCC [92]. Neoantigens are proteins that are produced during cellular events such as gene mutation and they are immunogenic [92].…”

Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments

“…Immunotherapy has revolutionized cancer treatments by minimizing adverse events, attacking the cancer microenvironment, and increasing the overall patient survival rate [ 1 ]. The aim of immunotherapy is to boost patients´ own T-cell immunity to recognize and eradicate the tumor [ 2 , 3 , 4 , 5 ]. Cancer vaccines are an attractive alternative immunotherapy option, where antigens from the tumor are selected and injected back into the patient to induce a highly targeted antitumor immune reaction [ 4 , 6 ].…”