Clinical approval: Trials of an anticancer jab

Clayton, Julie

doi:10.1038/488s4a

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…Phase III clinical trials have been completed for some years now with participants returning to normal health care systems making long‐term tracking more difficult. However, Scandinavian countries such as Finland have national registries that should enable follow‐up in these cohorts into the future . One study addressing memory responses looked at patients given a monovalent HPV16 L1 vaccine 8.5 years prior to challenge with the quadravalent HPV vaccine .…”

Section: Prophylactic Vaccinesmentioning

confidence: 99%

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

McKee

Bergot

Leggatt

2015

Reviews in Medical Virology

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It has been more than 7 years since the commercial introduction of highly successful vaccines protecting against highrisk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus-like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012. Copyright © 2015 John Wiley & Sons, Ltd. INTRODUCTIONTargeting cancers for immunotherapy is often complicated by a lack of immunogenic tumour peptides. Mutated or overexpressed self-antigens are frequently the targets and invoke a generally low affinity/avidity T and B cell response. In contrast, the tight association between infection with HPV and cervical cancer means that foreign viral proteins encoded by HPV can provide the basis of either prophylactic or therapeutic cancer vaccines [1,2]. The natural course of anogenital HPV infection results in overwhelming clearance of the virus in 98% of individuals with an immune component suggested by the increased risk of HPV-associated cancers in immune-compromised organ transplant recipients [3,4]. However, HPV genotype-specific antibodies against the viral capsid proteins (L1 and L2) are produced at only low levels in about half the patients, can take close to a year to develop after natural infection and associate with higher viral loads in the cervix [5]. Thus, natural antibody may reflect the non-lytic, localised, intracellular nature of the infection leading to poor immunogenicity for immunoglobulin production and a greater emphasis on T-cell immunity for viral clearance. In contrast, prior immunization with HPV capsid proteins in animal studies induces high titres of antibody that are protective against challenge infection. Early studies in dogs demonstrated that prior immunization with L1 capsid protein could protect beagles from mucosal challenge with canine oral ...

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Section: Prophylactic Vaccinesmentioning

confidence: 99%

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

McKee

Bergot

Leggatt

2015

Reviews in Medical Virology

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“…These oncogenic HPVs are also common risk factors in some other cancers, such as head and neck cancers [ 6 ]. However, there are still gaps in the knowledge of cervical cancer to answer the question of why HPV is necessary to cause cell carcinoma, although it is not a sufficient requirement [ 1 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

KF-finder: identification of key factors from host-microbial networks in cervical cancer

Gao

Zheng

et al. 2018

BMC Syst Biol

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BackgroundThe human body is colonized by a vast number of microbes. Microbiota can benefit many normal life processes, but can also cause many diseases by interfering the regular metabolism and immune system. Recent studies have demonstrated that the microbial community is closely associated with various types of cell carcinoma. The search for key factors, which also refer to cancer causing agents, can provide an important clue in understanding the regulatory mechanism of microbiota in uterine cervix cancer.ResultsIn this paper, we investigated microbiota composition and gene expression data for 58 squamous and adenosquamous cell carcinoma. A host-microbial covariance network was constructed based on the 16s rRNA and gene expression data of the samples, which consists of 259 abundant microbes and 738 differentially expressed genes (DEGs). To search for risk factors from host-microbial networks, the method of bi-partite betweenness centrality (BpBC) was used to measure the risk of a given node to a certain biological process in hosts. A web-based tool KF-finder was developed, which can efficiently query and visualize the knowledge of microbiota and differentially expressed genes (DEGs) in the network.ConclusionsOur results suggest that prevotellaceade, tissierellaceae and fusobacteriaceae are the most abundant microbes in cervical carcinoma, and the microbial community in cervical cancer is less diverse than that of any other boy sites in health. A set of key risk factors anaerococcus, hydrogenophilaceae, eubacterium, PSMB10, KCNIP1 and KRT13 have been identified, which are thought to be involved in the regulation of viral response, cell cycle and epithelial cell differentiation in cervical cancer. It can be concluded that permanent changes of microbiota composition could be a major force for chromosomal instability, which subsequently enables the effect of key risk factors in cancer. All our results described in this paper can be freely accessed from our website at http://www.nwpu-bioinformatics.com/KF-finder/.

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