ABSTRACT
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and therapeutic cancer vaccines have emerged as a promising immunotherapeutic strategy. These vaccines target tumor-associated antigens such as glypican-3, alpha-fetoprotein, melanoma-associate antigen-1, heat shock protein 70, glutamine synthetase, and TMEM176A/B, which are abnormally expressed in HCC cells and serve as both diagnostic markers and therapeutic targets. Various vaccine platforms—including peptide-based, dendritic cells-based, viral vector-based, and genetic vaccines (DNA/mRNA)—are under investigation for their ability to elicit antigen-specific cytotoxic T cell responses and establish long-term immune memory. Despite promising preclinical and early clinical results, challenges such as the immunosuppressive tumor microenvironment, antigen heterogeneity, and immune evasion mechanisms limit their efficacy. Future strategies focus on combination therapies with immune checkpoint inhibitors, personalized neoantigen vaccines, and advanced delivery technologies. These approaches aim to enhance immunogenicity and clinical outcomes, positioning therapeutic cancer vaccines as a key component of precision oncology in HCC.
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KEYWORDS: Hepatocellular carcinoma; Cancer vaccine; Therapeutic; Antigen
INTRODUCTION
Hepatocellular carcinoma (HCC) is a highly prevalent and lethal form of liver cancer, commonly associated with chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) [
1-
3]. Although conventional treatment modalities such as surgical resection, chemotherapy—including molecularly targeted agents—and radiotherapy have evolved, therapeutic outcomes for advanced HCC remain suboptimal [
4,
5]. In recent years, immunotherapy has emerged as a transformative approach in HCC management. Notably, immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape, with the combination of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) now established as a first-line therapy for advanced HCC [
6]. This regimen has demonstrated a median overall survival of approximately 19 months and an objective response rate of 30%, reflecting its clinical significance. Ongoing basic and clinical investigations are further expanding the immunotherapeutic toolkit, encompassing novel modalities such as adoptive cell therapy and cancer vaccines [
7]. Therapeutic vaccines, designed to stimulate tumor-specific immune responses, are currently in early developmental stages but hold considerable promise as future components of HCC treatment [
8-
11]. These advances collectively highlight a paradigm shift toward immune-based strategies aimed at improving long-term survival and disease control.
This review provides a comprehensive overview of the current status, limitations, and future directions of therapeutic cancer vaccines in HCC, highlighting their potential role in precision oncology and synergistic immunotherapy.
MAJOR TU MOR-ASSOC IATED ANT IGENS (TAAs) FROM HCC
In HCC, TAAs are proteins that are overexpressed or abnormally expressed in cancer cells. These antigens are recognized by the immune system and can be used as targets for cancer diagnosis and treatment. Major TAAs include the following (
Table 1):
GPC-3 is a membrane-associated proteoglycan that plays a significant role in HCC [
12]. It is predominantly expressed in the placenta and fetal liver, with limited expression in adult tissues [
12]. Its re-expression in HCC and secretion into the serum make it a valuable diagnostic marker [
12,
13]. GPC-3 is involved in several key signaling pathways, including Wnt, insulin-like growth factor (IGF), Yes-associated protein (YAP), and Hedgehog, which contribute to tumor proliferation, metastasis, apoptosis resistance, and epithelial-mesenchymal transition (EMT).
Approximately 80% of HCC cases show overexpression of GPC-3, while it is rarely observed in normal liver tissues, making it a specific marker for HCC diagnosis [
12]. Moreover, it helps differentiate HCC from other hepatic diseases [
12]. High levels of GPC-3 are associated with aggressive tumor behavior and poor prognosis, including reduced overall and disease- free survival [
14]. Therapeutically, GPC-3 has emerged as a promising target for various modalities, such as monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapies, and peptide-based vaccines. These strategies aim to inhibit tumor progression and improve clinical outcomes [
12,
13]. Collectively, the unique expression profile and oncogenic role of GPC-3 underscore its potential as both a diagnostic biomarker and a therapeutic target in HCC [
12].
AFP is a well-established serum biomarker for HCC, and is currently under investigation as a target for vaccine-based immunotherapy [
15,
16]. AFP-based vaccines are designed to stimulate the host immune system to recognize and eliminate AFP-expressing HCC cells, primarily through the induction of AFP-specific CD8⁺ cytotoxic T lymphocytes (CTLs) [
15].
Recent studies indicate that combining AFP vaccines with ICIs—particularly anti-PD-L1 antibodies—can substantially suppress HCC progression, as demonstrated in preclinical models [
15]. This combination approach enhances immune activation and may improve therapeutic efficacy. Clinical trials have been conducted to evaluate the safety, immunogenicity, and potential efficacy of AFP peptide immunization in HCC patients. These investigations focus on the ability of AFP vaccines to initiate a robust immune response and mediate tumor cell killing [
17]. Despite their promise, AFP-based vaccines face challenges such as immune cell exhaustion and suboptimal response rates. Strategic integration with other immunotherapeutic agents may offer a pathway to overcome these limitations and maximize clinical benefit [
16]. Overall, AFP vaccines represent a promising direction in HCC management, particularly when administered in combination with synergistic therapies that enhance anti-tumor activity [
15,
17].
MAGE-1 is currently being investigated as a potential target for vaccine-based immunotherapy in HCC [
18]. MAGE-1-based vaccines are designed to activate the immune system by inducing MAGE-1-specific CD8⁺ CTLs, thereby enabling targeted recognition and destruction of MAGE-1-expressing HCC cells [
19]. Emerging evidence from preclinical studies suggests that combining MAGE-1 vaccines with ICIs, such as anti-programmed cell death protein 1 (PD-1) antibodies, significantly enhances tumor clearance and improves survival outcomes [
19]. This combinatorial strategy holds promise for achieving synergistic antitumor effects.
Clinical trials have been initiated to assess the safety and efficacy of MAGE-1-directed T cell receptor-engineered (TCR-T) cell therapies in patients with advanced or metastatic MAGE-1-positive malignancies, including HCC [
18]. These studies aim to validate the therapeutic potential of MAGE-1 targeting in real-world patient populations. Taken together, MAGE-1 vaccines represent a promising avenue for HCC treatment, particularly when used in concert with other immunotherapies to amplify immune response and improve clinical outcomes [
19].
HSP70 is being actively investigated as a novel target for vaccine-based immunotherapy in HCC [
20]. HSP70-based vaccines are designed to stimulate an immune response through the activation of HSP70-specific CTLs, which selectively recognize and eliminate HSP70-expressing tumor cells [
20]. Preclinical studies have demonstrated that the combination of HSP70 vaccines with other immunotherapeutic agents—particularly ICIs—can markedly enhance the antitumor immune response and improve therapeutic efficacy [
20]. This combinatorial approach may offer a synergistic effect, increasing the potency of vaccine-mediated tumor elimination.
Currently, clinical trials are underway to assess the safety, immunogenicity, and therapeutic potential of HSP70-based vaccines in HCC patients. These studies are focused on evaluating how effectively the vaccines elicit immune activation and reduce tumor burden [
21].
Given its tumor-specific expression and immunostimulatory properties, HSP70 represents a promising therapeutic target in HCC. When administered alongside other immunotherapies, HSP70-based vaccines may enhance treatment outcomes and broaden the scope of personalized cancer immunotherapy [
20,
21].
GS is being actively explored as a novel target for vaccine-based immunotherapy in HCC [
22]. GS-based vaccines are designed to activate GS-specific CTLs, which are capable of recognizing and eliminating GS-expressing HCC cells [
22]. Recent studies have demonstrated that combining GS-targeted vaccines with other immunotherapeutic agents, particularly ICIs, can potentiate the antitumor immune response. Such combinatorial strategies have shown enhanced vaccine efficacy in preclinical settings [
23].
Currently, clinical trials are underway to evaluate the safety, immunogenicity, and therapeutic potential of GS-based vaccines in patients with HCC. These trials aim to determine the degree of immune activation elicited by the vaccine and its subsequent impact on tumor control [
24]. Taken together, GS-directed vaccine therapy represents a promising approach for HCC treatment, especially when integrated with other immunotherapies to synergistically improve clinical outcomes [
22-
24].
Transmembrane proteins TMEM176A and TMEM176B have emerged as novel immunoregulatory targets for vaccine-based therapies in HCC [
25]. TMEM176A/B-based vaccines are designed to activate the immune system by stimulating TMEM176A/B-specific CTLs, thereby promoting immune recognition and elimination of HCC cells expressing these proteins [
25]. Both TMEM176A and TMEM176B play a role in modulating immune responses, and recent research has highlighted that combining TMEM176A/B-targeted vaccines with ICIs—particularly nivolumab—can enhance antitumor activity and improve the effectiveness of checkpoint blockade therapy [
25]. This synergistic combination has shown encouraging outcomes in preclinical investigations.
Ongoing clinical trials are assessing the safety, immunogenicity, and therapeutic efficacy of TMEM176A/B-based vaccines in patients with HCC. These studies aim to determine the degree to which such vaccines stimulate immune activation and suppress tumor progression [
26]. Taken together, TMEM176A/B-targeted vaccines represent a promising immunotherapeutic strategy for HCC, especially when integrated with other treatment modalities to augment clinical benefit [
25,
26].
CURRENT STATUS OF CANCER VACCINES IN HCC
Types of Cancer Vaccines
Therapeutic cancer vaccines are designed to stimulate the host immune system to recognize and eradicate malignant cells while establishing durable immune memory against tumor antigens. These vaccines aim to treat existing cancers by enhancing antigen-specific immune responses, thereby contributing to tumor control and potential remission [
9,
27]. Notable examples include dendritic cells (DCs)-based vaccines and peptide-based vaccines, both of which have demonstrated immunogenicity and clinical promise in various cancer types [
9,
27].
In contrast, prophylactic vaccines are intended to prevent cancer development by priming the immune system in individuals who are tumor-free. These vaccines are primarily utilized to prevent malignancies associated with oncogenic viral infections, such as HBV and human papillomavirus, which are well-known risk factors for HCC and cervical cancer, respectively [
9].
Peptide-based vaccines employ synthetic peptides that correspond to TAAs, such as GPC-3 and AFP, which are commonly overexpressed in HCC [
28,
29]. These vaccines are designed to elicit antigen-specific T cell responses, contributing to tumor cell eradication. Clinical trials have reported encouraging outcomes in terms of immunogenicity and survival benefit (
Table 2) [
28,
29].
DCs-based vaccines harness the antigen-presenting capabilities of DCs to prime the immune system against tumor antigens. In this approach, autologous DCs are extracted, loaded ex vivo with HCC-specific antigens, and re-administered to the patient to stimulate robust T cell activation. This strategy has demonstrated favorable safety profiles and therapeutic efficacy in early-phase clinical studies involving HCC patients [
30].
Viral vector-based vaccines utilize engineered viruses—such as adenovirus and vesicular stomatitis virus—to deliver tumor antigens directly to immune cells [
9]. These platforms are capable of inducing potent and sustained immune responses, and are being actively explored for their application in HCC immunotherapy.
Genetic vaccines, including DNA and messenger RNA (mRNA) platforms, encode tumor antigens within plasmid DNA or synthetic mRNA constructs [
31]. Following administration, host cells translate these sequences into antigens that are subsequently presented to the immune system, initiating targeted immune activation. While DNA vaccines have shown potential in preclinical and clinical models, mRNA vaccines are gaining particular attention for their ability to provoke strong antigen-specific immune responses and ease of manufacturing [
31].
THERAPEUTIC CANCER VACCINES
Principle
Therapeutic cancer vaccines are developed to induce a targeted immune response against malignant cells by exploiting the specificity of TAAs or tumor-specific antigens (TSAs) [
32]. These antigens are selectively expressed on cancer cells but absent in normal tissues, allowing the immune system to distinguish neoplastic cells from healthy counterparts [
32].
By presenting these tumor antigens to the host immune system, therapeutic vaccines aim to activate various immune effector cells—including CTLs and antigen-presenting cells—to mount a robust and sustained response against tumor cells [
32]. This immunological activation is critical to achieving tumor control and long-term immune surveillance.
Antigen presentation is a critical step in cancer vaccine-mediated immune activation. The vaccine introduces TAAs or TSAs to the host immune system using various platforms, including peptide-based, cell-based, viral vector-based, and nucleic acid-based vaccines [
32]. These antigens are internalized by professional antigen-presenting cells (APCs), particularly DCs, which process and display them on their surface through major histocompatibility complex (MHC) molecules to initiate immune recognition [
32].
Following antigen presentation, T cells—especially cytotoxic CD8⁺ T cells—are activated upon recognition of the MHC-peptide complexes. These effector cells play a pivotal role in identifying and eliminating tumor cells expressing the corresponding antigens, thereby contributing to tumor regression and improved immune surveillance [
32].
Importantly, cancer vaccines facilitate the generation of long-term immune memory by training the immune system to recognize and respond to tumor antigens upon recurrence. This immunological memory is essential for sustained cancer control and prevention of relapse [
33].
Therapeutic cancer vaccines are designed to target specific TAAs, including AFP, GPC-3, and others that are commonly overexpressed in HCC [
33]. Although these vaccines remain largely within the experimental and clinical trial stages, accumulating evidence supports their potential to enhance antigen-specific immune responses and contribute to tumor control [
33].
A variety of vaccine platforms are currently under investigation through clinical trials to assess their safety and therapeutic efficacy in HCC patients. These include peptide-based vaccines, DCs-based vaccines, viral vector-based vaccines, and nucleic acid-based vaccines, each offering distinct mechanisms for antigen delivery and immune activation [
9].
LIMITATIONS OF THERAPEUTIC CANCER VACCINES IN HCC
Tumor Immune Microenvironment (TME)
HCC frequently establishes an immunosuppressive TME that impairs the efficacy of therapeutic cancer vaccines [
34]. This immunoregulatory milieu is characterized by the presence of immunosuppressive cell populations such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as immunosuppressive cytokines including interleukin-10 and transforming growth factor-beta, all of which contribute to the attenuation of antitumor immune responses [
34].
The intricate cellular interactions and signaling networks within this microenvironment promote immune evasion and tumor progression, thereby limiting the capacity of vaccines to generate robust cytotoxic T cell-mediated responses [
34]. Moreover, the liver’s immunological uniqueness—marked by continuous exposure to gut-derived antigens, chronic inflammation, and persistent infections such as HBV and HCV—further complicates vaccine-induced immune activation and promotes immune tolerance [
35].
The selection of optimal TAAs for vaccine development in HCC poses significant challenges due to their variable immunogenicity and expression profiles [
36]. Not all TAAs are capable of eliciting robust and specific immune responses, and certain antigens may be expressed in normal tissues, thereby increasing the risk of off-target effects and potential toxicity [
36].
Therefore, careful antigen selection is essential to ensure specificity toward malignant cells and minimize adverse outcomes. Antigens must exhibit restricted expression in normal tissues while retaining strong immunostimulatory potential. For instance, GPC-3 has been identified as a promising candidate due to its overexpression in HCC; however, its baseline expression in select normal tissues necessitates thorough evaluation to avoid unintended immunologic consequences [
36].
Cancer cells, including those in HCC, possess the ability to develop immune evasion mechanisms that undermine the effectiveness of therapeutic vaccines [
34]. A common strategy involves the downregulation of antigen presentation machinery, MHC molecules, which are essential for T cell recognition. Reduced MHC expression impairs the immune system’s ability to identify and eliminate tumor cells [
34].
Furthermore, HCC cells exploit immune checkpoint pathways to dampen antitumor immunity. In particular, the expression of inhibitory receptors such as PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on activated T cells can lead to T cell exhaustion and functional suppression [
34]. These checkpoints are co-opted by tumor cells to escape immune surveillance and establish persistent growth.
Together, these immune evasion strategies present significant barriers to sustained vaccine efficacy and highlight the need for combinatorial approaches—such as checkpoint blockade—in cancer immunotherapy.
Clinical Outcomes
Although therapeutic cancer vaccines have demonstrated promising immunogenicity in preclinical studies, their translation into meaningful clinical outcomes remains limited in large-scale trials [
37]. This discrepancy can be attributed to interpatient variability and the biological complexity of HCC, which includes factors such as tumor heterogeneity, immune landscape diversity, and individual immune competence [
37].
These challenges have been exemplified in ongoing clinical investigations such as the HepaVac-101 [
38] and GNOSPV02 [
39] trials. In the HepaVac-101 trial, vaccine-specific T-cell responses were observed in 68.4% of patients, with 36.8% responding to at least one class I TUMAP and 52.6% responding to at least one class II TUMAP, while the safety profile was favorable with only transient grade 1–2 injection-site reactions reported [
38]. In the GNOS-PV02 phase 1/2 study, neoantigens co-administered with plasmid-encoded interleukin-12 and pembrolizumab in patients with advanced HCC demonstrated an objective response rate (RECIST 1.1) of 30.6% (11 of 36 patients), including 8.3% complete responses, and neoantigen-specific T-cell responses were observed in 86.4% of evaluable patients [
39]. While these studies have shown preliminary signs of efficacy, they also underscore the necessity for further vaccine optimization and larger randomized trials to validate clinical benefit and reproducibility.
The production and delivery of therapeutic cancer vaccines present considerable technical and logistical challenges [
37]. Manufacturing processes must be rigorously controlled to ensure consistency in vaccine potency, purity, and safety across different production batches and among diverse patient populations [
37]. Maintaining such standards is essential to achieving reproducible clinical outcomes and regulatory compliance.
Additionally, effective delivery systems are required to ensure that therapeutic vaccines reach and activate target immune cells in vivo. Platforms such as nanoparticle carriers, viral vectors, and electroporation-enhanced injection techniques have been developed to optimize antigen delivery and uptake [
9,
29].
Personalized cancer vaccines, which are designed to match the unique antigenic profile of an individual’s tumor, further complicate the manufacturing landscape. These vaccines require sophisticated technologies including next-generation sequencing, neoantigen prediction algorithms, and custom formulation processes to enable individualized therapeutic solutions [
9,
29].
FUTURE DIRECTIONS IN THERAPEUTIC CANCER VACCINES FOR HCC
Combination Therapies
The integration of cancer vaccines with conventional treatment modalities—such as chemotherapy, radiotherapy, and ICIs—has demonstrated potential in enhancing therapeutic efficacy in HCC [
27]. This multimodal approach leverages complementary mechanisms to amplify antitumor immune responses and overcome tumor-induced immune suppression.
Notably, combining therapeutic vaccines with ICIs, including PD-1 and PD-L1 blockade agents, can counteract immune evasion strategies employed by HCC cells and restore T cell functionality [
40]. Furthermore, traditional therapies like chemotherapy and radiotherapy can modulate the tumor microenvironment, increasing antigen presentation and rendering cancer cells more susceptible to immune-mediated destruction [
27].
This synergistic approach aims to optimize clinical outcomes by enhancing immune activation, reducing tumor burden, and improving overall patient survival rates [
41].
The development of personalized cancer vaccines tailored to individual tumor profiles represents a promising approach to enhance both specificity and therapeutic efficacy in HCC [
42]. These vaccines utilize TSAs and neoantigens that are unique to each patient's malignancy, thereby enabling a precise and patient-customized immune response [
42].
Technological advancements in next-generation sequencing and bioinformatics have facilitated the rapid identification of personalized antigenic targets, paving the way for vaccine formulations that are highly specific to the molecular landscape of each tumor [
43]. Such precision immunotherapy has been supported by clinical data demonstrating robust immunogenicity and improved treatment outcomes.
For instance, neoantigen-based vaccines have shown encouraging results in clinical trials, including prolonged progression-free survival in patients with melanoma and non-small cell lung cancer, thereby validating the potential of personalized vaccine strategies in oncology [
44].
Recent advances in vaccine platforms and adjuvant design are pivotal to enhancing immune responses and overcoming the immunosuppressive microenvironment commonly observed in HCC [
45]. Innovative delivery platforms—including mRNA, DNA, and viral vector-based vaccines—are being intensively investigated for their capacity to induce potent and durable antigen-specific immune responses [
45].
To augment vaccine efficacy, novel adjuvants are under development that can more effectively stimulate the immune system and optimize antigen presentation [
46]. Particularly promising are adjuvants targeting innate immune receptors such as Toll-like receptors (TLRs) and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which promote DCs activation and enhance T cell priming [
47].
These technological advancements are expected to not only improve the clinical effectiveness of therapeutic cancer vaccines but also broaden their applicability across diverse cancer types [
48].
Conducting robust and extensive clinical trials is imperative to validate the efficacy and safety of emerging therapeutic cancer vaccine candidates [
49]. These trials follow a phased approach to ensure rigorous evaluation prior to clinical adoption. Phase I trials primarily assess safety and immunogenicity in a small cohort of participants, while Phase II trials expand to larger populations to evaluate therapeutic efficacy and monitor adverse effects. Phase III trials involve large-scale enrollment to confirm effectiveness and detect rare or long-term side effects under real-world conditions [
49].
systematic progression is essential for advancing cancer vaccine development and ensuring that new therapies meet regulatory standards and clinical utility. For instance, the HepaVac-101 trial represents a pivotal effort in evaluating a personalized cancer vaccine for HCC, with early-phase data demonstrating promising immunogenicity and safety profiles [
38].
HCC remains a prevalent and aggressive form of liver cancer with limited therapeutic options, particularly in advanced stages. Therapeutic cancer vaccines have emerged as a promising modality that harnesses the immune system to selectively target and eliminate tumor cells. These vaccines aim to induce antigen-specific immune responses and establish long-term immunological memory capable of preventing recurrence.
A diverse array of vaccine platforms is under active investigation, including peptide-based, DCs-based, viral vector-based, and nucleic acid-based (DNA and mRNA) vaccines. Each platform offers distinct mechanisms for antigen delivery and immune activation, enabling tailored strategies for immunotherapy in HCC.
Nevertheless, vaccine development faces notable challenges. tumor heterogeneity complicates antigen selection, while the immunosuppressive liver microenvironment—comprising Tregs, MDSCs, and inhibitory cytokines—limits immune activation and promotes tumor immune escape. Furthermore, cancer cells may downregulate MHC expression and exploit immune checkpoints such as PD-1 and CTLA-4, further hindering vaccine efficacy.
Despite these barriers, therapeutic vaccines have demonstrated the capacity to reshape the immune landscape of HCC. Combination therapies that incorporate ICIs, chemotherapy, or radiotherapy have shown synergistic effects, enhancing antitumor responses and improving clinical outcomes. Trials like HepaVac-101 exemplify the potential of personalized cancer vaccines tailored to individual tumor profiles.
Future directions in HCC immunotherapy focus on precision medicine approaches, including neoantigen-driven vaccine design, advanced antigen delivery platforms, novel adjuvants targeting innate immunity pathways (e.g., TLRs, cGAS-STING), and biomarker-guided patient stratification. These innovations are expected to overcome current limitations and expand the applicability of cancer vaccines across heterogeneous tumor populations.
CONCLUSION
Despite the considerable challenges associated with the development of effective therapeutic vaccines for HCC, the potential clinical benefits are compelling. The strategic integration of combination therapies, precision medicine approaches, and innovative vaccine platforms offers a promising pathway to enhance tumor-specific immune responses and improve clinical outcomes in HCC patients. Overcoming barriers such as tumor heterogeneity, immunosuppressive microenvironments, and immune evasion mechanisms will require continued translational research and multidisciplinary collaboration. Extensive, well-designed clinical trials are essential to validate the safety, efficacy, and long-term benefits of emerging vaccine candidates.
As the field advances, personalized immunotherapeutic strategies and cutting-edge delivery technologies are expected to reshape HCC treatment paradigms, ultimately contributing to improved survival and quality of life for patients affected by this challenging malignancy.
NOTES
-
ACKNOWLEDGEMENTS
None.
-
FUND
This work was supported by clinical research grant from Pusan National University Hospital in 2023.
-
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
-
AUTHOR CONTRIBUTIONS
Jeong Heo conceptualized the study. Jeong Heo and Hyun Young Woo contributed to manuscript writing.
Table 1.Strategic vaccine targets in hepatocellular carcinoma
Table 1.
|
Target |
Mechanism |
Combination therapy |
Clinical trials |
Potential |
|
Glypican-3 (GPC-3) |
Involved in signaling pathways like Wnt, IGF, YAP, Hedgehog. Inhibits tumor growth |
Therapies like monoclonal antibodies, CAR-T cells, GPC-3 vaccines aim for clinical improvement |
Focused on its role as a diagnostic marker and treatment through targeted immunotherapy |
High specificity in HCC diagnosis; promising therapeutic target |
|
Alpha-fetoprotein (AFP) |
Stimulates immune response using AFP-specific CD8+ T cells |
Combining AFP vaccines with anti-PD-L1 immune checkpoint inhibitors enhances therapy |
Tested in preclinical models and clinical trials for inducing immune responses to kill tumors |
Effective in combination therapies; faces challenges like immune exhaustion |
|
Melanoma antigen gene-1 (MAGE-1) |
Induces MAGE-1-specific CD8+ T cells to target cancer cells |
Combined with anti-PD-1 inhibitors for increased survival and tumor clearance |
MAGE-1-directed TCR-T cell therapy evaluated in advanced/metastatic tumor clinical trials |
Enhanced effectiveness with immunotherapies; promising for metastatic cases |
|
Heat shock protein 70 (HSP70) |
Generates CTLs targeting HSP70-expressing tumor cells |
Enhanced immune response when combined with therapies like immune checkpoint inhibitors |
Ongoing trials focus on vaccineinduced immune activation and impact on tumor control |
Strong immune activation; complementary with other therapies |
|
Glutamine synthetase (GS) |
Produces CTLs to kill GS-expressing cancer cells |
Immune checkpoint inhibitors improve vaccine efficacy and antitumor response |
Evaluated for immune response and tumor suppression in clinical trials |
Promising immune-targeted therapy when combined with immunotherapies |
|
TMEM176A/B |
Modulates immune responses against TMEM176A/B-positive HCC cells |
Combined with nivolumab for enhanced antitumor response and checkpoint inhibitor effectiveness |
Trials assess safety, immune modulation, and therapeutic impact on tumor progression |
Novel regulatory targets with therapeutic potential in combination immunotherapy strategies |
Table 2.Platforms for HCC vaccine development
Table 2.
|
Vaccine platform |
Mechanism |
Key features |
Clinical insights |
|
Peptide-based vaccines |
Utilize specific peptides to target TAAs like GPC-3 and AFP |
Trigger immune responses by targeting overexpressed TAAs in HCC |
Clinical trials show promising results in eliciting immune responses and improving survival rates |
|
Dendritic cells-based vaccines |
Isolate patient’s dendritic cells, load them with tumor antigens, and reintroduce them |
Activates T cells via potent antigen-presenting dendritic cells |
Demonstrated safety and efficacy in HCC clinical trials |
|
Viral vector-based vaccines |
Use engineered viruses (e.g., adenovirus, vesicular stomatitis virus) to deliver antigens |
Induce strong and durable immune responses through viral vectors |
Explored for robust immune stimulation against HCC antigens |
|
DNA and mRNA vaccines |
Introducing genetic material (DNA or mRNA) to instruct cells to produce tumor antigens |
DNA encodes tumor antigens; mRNA produces antigens within cells, inducing potent immune responses |
Preclinical and clinical studies show promise, with mRNA gaining attention for its effectiveness |
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