Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma

Boozari, B.; Mundt, Bettina; Woller, Norman; Strüver, N.; Gürlevik, Engin; Schache, Peter; Kloos, Arnold; Knocke, Sarah; Manns, Michael P.; Wirth, Thomas; Kubicka, Stefan; Kühnel, Florian

doi:10.1136/gut.2009.196519

Cited by 54 publications

(48 citation statements)

References 43 publications

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“…Results of all these endeavours are eagerly awaited as well as the final incorporation of immune cancer control as a potential therapeutic option. 133134 …”

Section: Treatment: Current Challenges and Future Perspectivesmentioning

confidence: 99%

Hepatocellular carcinoma: clinical frontiers and perspectives

Bruix

Gores

Mazzaferro

2014

Gut

1,227

1,049

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies.

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“…Results of all these endeavours are eagerly awaited as well as the final incorporation of immune cancer control as a potential therapeutic option. 133134 …”

Section: Treatment: Current Challenges and Future Perspectivesmentioning

confidence: 99%

Hepatocellular carcinoma: clinical frontiers and perspectives

Bruix

Gores

Mazzaferro

2014

Gut

1,227

1,049

View full text Add to dashboard Cite

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“…Unfortunately, its therapeutic efficacy appears disappointing in clinical trials, and a standard therapeutic method has not been established. Recently, attention has focused on a variety of vaccines investigated in experimental studies comprising patients with HCC, because they have been reported to greatly induce a tumorspecific immune response against tumor cells (4,5). As a result, identifying and establishing a novel approach for the prevention of HCC development and recurrence (i.e.…”

mentioning

confidence: 99%

Anticancer Drugs Cause Release of Exosomes with Heat Shock Proteins from Human Hepatocellular Carcinoma Cells That Elicit Effective Natural Killer Cell Antitumor Responses in Vitro

Wan

Lin

et al. 2012

Journal of Biological Chemistry

410

317

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Background: Exosome is a novel secretory pathway for HSPs, which induce antitumor responses. Results: Anticancer drugs caused release of HSP-bearing exosomes by HepG2 cells and elicited efficient NK cell antitumor responses. Conclusion: Exosomes derived from hepatocellular carcinoma cell-resistant anticancer drug-treated HepG2 cells conferred superior immunogenicity in inducing HSP-specific NK cell responses. Significance: Exosomes provided a clue for finding an efficient vaccine for HCC immunotherapy.

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“…Although the exact mechanisms of these immunotherapies are not fully clear, it has been reported that CTLA-4 inhibition led to expansion of CD8 T cells directed against mutated tumor epitopes (46,47). CD8 T-cell responses are also important mediators of antitumor cytotoxicity following virotherapy whereby effective oncolytic inflammation in the tumor tissue is an important precondition to fully exploit these promising functions (10,48,49). The sum of proteinencoded mutations of a single tumor, the mutanome, provides an attractive pool of neoantigenic targets that can be rationally predicted by tumor exome sequencing and algorithm-based search (46,50).…”

Section: Discussionmentioning

confidence: 99%

PolySia-Specific Retargeting of Oncolytic Viruses Triggers Tumor-Specific Immune Responses and Facilitates Therapy of Disseminated Lung Cancer

Kloos

Woller

Gürlevik

et al. 2015

Cancer Immunology Research

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Polysialic acid (polySia) is expressed on several malignant tumors of neuroendocrine origin, including small cell lung cancer. In this study, we investigated the therapeutic efficacy of tumor-directed T-cell responses, elicited by polySia-retargeted oncolytic adenovirus infection, in an orthotopic murine model of disseminated polySia-positive lung cancer. In several cell lines, we demonstrated highly polySia-selective retargeting of adenoviral infection using a bispecific adapter comprising the ectodomain of the coxsackievirus/adenovirus receptor and a polySia-recognizing single-chain antibody domain. PolySiadependent systemic infection in vivo facilitated effective uptake of viruses in subcutaneous polySia-expressing human tumors, whereas hepatic viral load and hepatotoxicity were significantly reduced. The impact and nature of antitumoral immune responses triggered by systemic delivery of polySia-retargeted oncolytic adenoviruses were investigated in an orthotopic model of disseminated lung cancer. Interestingly, improved transduction by polySia-retargeted oncolytic adenoviruses led to CD45-positive cell infiltrates in close association with large lytic areas. Consistently, enhanced tumor regression and prolonged survival was only observed in immunocompetent mice, but not in T-celldeficient mice. To investigate whether improved systemic infection by polySia retargeting would elicit a tumor-specific T-cell response, we screened the used lung cancer cells for mutated oncogenes by complete exon sequencing. In agreement with our other results, only retargeted oncolysis was able to induce a significant response specific for the tumor-associated neoepitope Gsta2-Y9H. In conclusion, we demonstrated that effective retargeting of oncolytic adenovirus against polySia-expressing tumors elicits an effective tumor-directed T-cell response after systemic virus delivery and facilitates therapy of disseminated lung cancer.

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Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma

Cited by 54 publications

References 43 publications

Hepatocellular carcinoma: clinical frontiers and perspectives

Hepatocellular carcinoma: clinical frontiers and perspectives

Anticancer Drugs Cause Release of Exosomes with Heat Shock Proteins from Human Hepatocellular Carcinoma Cells That Elicit Effective Natural Killer Cell Antitumor Responses in Vitro

PolySia-Specific Retargeting of Oncolytic Viruses Triggers Tumor-Specific Immune Responses and Facilitates Therapy of Disseminated Lung Cancer

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