Immunopreventive Effects against Murine H22 Hepatocellular Carcinoma in vivo by a DNA Vaccine Targeting a Gastrin-Releasing Peptide

Meko'o, Jean Louis Didier; Xing, Yun; Zhang, Huiyong; Lu, Yue; Wu, Jie; Cao, Ruihua

doi:10.7314/apjcp.2014.15.20.9039

Cited by 5 publications

(5 citation statements)

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“…Currently, liver cancer vaccines are primarily categorized as preventive and therapeutic types, with the main goal of initiating or enhancing the human body’s immune response against cancer. 28 Some preventive vaccines, such as DNA vaccines, 29 live-attenuated Listeria vaccines 30 and peptide vaccine 31 have shown effective preventive results. On the other hand, personalized peptide vaccines have demonstrated efficacy in postoperative liver cancer prevention, 32 but their effectiveness varies due to individual patient characteristics and the heterogeneity of HCC.…”

Section: Discussionmentioning

confidence: 99%

Drug-Loaded Tumor-Derived Microparticles Elicit CD8+ T Cell-Mediated Anti-Tumor Response in Hepatocellular Carcinoma

Chen,

Zhang,

Wang

et al. 2024

IJN

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Background Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment. Methods Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities. Results Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine. Conclusion Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine.

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Section: Discussionmentioning

confidence: 99%

Drug-Loaded Tumor-Derived Microparticles Elicit CD8+ T Cell-Mediated Anti-Tumor Response in Hepatocellular Carcinoma

Chen,

Zhang,

Wang

et al. 2024

IJN

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“…Gastrin-releasing peptide promotes hepatocellular carcinoma cell growth not only by interacting with homologous receptors of gastrin-releasing peptide co-expressed in tumor cells but also by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK1/2) pathway through a non-dependent mechanism of the epidermal growth factor receptor (EGFR) ( Savage et al, 2006 ), it can also inhibit the growth of normal liver cells by blocking the activation of ER ( Li et al, 2013 ). A DNA vaccine targeting gastrin-releasing peptide has been shown to inhibit the growth of blood vessels in liver tumors and to destroy tumor cells ( Meko’o et al, 2014 ; Stubbs et al, 2002 ). However, in cholangiocarcinoma, gastrin appears to have the opposite effect to that of hepatocellular carcinoma, inhibiting the proliferation of cholangiocarcinoma cells and inducing apoptosis via the Ca2+ dependent protein kinase C (PKC)-α pathway ( Kanno et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

“…CCK has functions that include stimulation of intestinal motility, stimulation of pancreatic enzyme secretion, and stimulation of gastric acid secretion ( Rehfeld, 2017 ). Its primary function is to trigger gallbladder emptying by binding to the CCK A-type receptor (CCKAR) and mediating the activation of post-membrane signaling pathways in smooth muscle, defects in CCKAR are a key point of impairment of gallbladder motility, which in turn may form the background for GBC ( Suzuki et al, 2001 ; Best Practice & Research Clinical Endocrinology & Metabolism, 2008 ), abnormal level of CCK results in reduced or delayed postprandial gallbladder contraction, leading to bile stagnation and creating an environment for cholesterol supersaturation and subsequent gallstone formation ( Savage et al, 2006 ; Meko’o et al, 2014 ; Stubbs et al, 2002 ; Kanno et al, 2001 ; Chau et al, 2006 ). Both CCK and its receptor CCKAR are important in the pathogenesis of biliary tract tumors, CCK is currently thought to exhibit growth-stimulating effects on biliary tract-derived cancer cell line ( Lee et al, 1989 ), an analysis of the biliary tract tumor in Shanghai, China, found that women with the CCKAR genotype were at increased risk of gallbladder cancer, and biliary tumorigenesis may be inhibited when CCKAR is in an antagonistic state ( Ogura et al, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

Using proton pump inhibitors increases the risk of hepato-biliary-pancreatic cancer. A systematic review and meta-analysis

Zhou

Chen²,

Fan³

et al. 2022

Front. Pharmacol.

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Background: More and more studies are focusing on the adverse effects and damage caused by PPI abuse, we carried out a systematic review and meta-analysis for assessing whether the proton pump inhibitor (PPI) leads to hepato-biliary-pancreatic cancer.Methods: PubMed, EMBASE and Web of Science were searched until 1 July 2022, 25 studies (17 case-control and 8 cohort studies; 2741853 individuals) included in this study. Pooled Odd Ratios (ORs) were used for random effect models. Sensitivity analysis and dose-response analysis, subgroup analysis were all conducted.Results: The aggregate OR of the meta-analysis was 1.69 (95% confidence interval (CI): 1.42–2.01, p = 0.01) and heterogeneity (I2 = 98.9%, p < 0.001) was substantial. According to stratified subgroup analyses, the incidence of hepato-biliary-pancreatic cancer was associated, expect for study design, study quality and region. Risk of hepato-biliary-pancreatic cancer is highest when people is treated with normal doses of PPI. The risks decrease and become insignificant when the cumulative defined daily dose (cDDD) increases.Conclusion: The use of PPI may be associated with an increased risk of hepato-biliary-pancreatic cancer. Hence, caution is needed when using PPIs among patients with a high risk of hepato-biliary-pancreatic cancer.

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“…Also, preventive vaccines have shown promising potential in the fight against HCC. One such example is a DNA vaccine targeting the B cell epitope GRP18-27, which demonstrated preventive effects against H22 hepatocarcinoma, paving the way for new immunotherapeutic approaches in liver cancer treatment [ 27 ]. Innovative approaches, such as using live-attenuated Listeria as a safe and efficient vaccine, have also shown the potential to induce protective immune responses in liver fibrosis and hepatobiliary malignancies [ 28 ].…”

Section: Cancer Vaccinementioning

confidence: 99%

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma

et al. 2023

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HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies.

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Immunopreventive Effects against Murine H22 Hepatocellular Carcinoma in vivo by a DNA Vaccine Targeting a Gastrin-Releasing Peptide

Abstract: There is a continuing need for innovative alternative therapies for liver cancer. DNA vaccines for hormone/ growth factor immune deprivation represent a feasible and attractive approach for cancer treatment.

Cited by 5 publications

References 28 publications

Drug-Loaded Tumor-Derived Microparticles Elicit CD8+ T Cell-Mediated Anti-Tumor Response in Hepatocellular Carcinoma

Drug-Loaded Tumor-Derived Microparticles Elicit CD8+ T Cell-Mediated Anti-Tumor Response in Hepatocellular Carcinoma

Using proton pump inhibitors increases the risk of hepato-biliary-pancreatic cancer. A systematic review and meta-analysis

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma

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