Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

• MeSH
• celogenomová asociační studie MeSH
• exprese genu MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• HLA antigeny klasifikace   genetika   imunologie   MeSH
• humorální imunita * MeSH
• infekce papilomavirem genetika   imunologie   patologie   virologie   MeSH
• kouření patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   patogenita   MeSH
• lokus kvantitativního znaku MeSH
• metaanalýza jako téma MeSH
• nádory orofaryngu genetika   imunologie   patologie   virologie   MeSH
• nádory úst genetika   imunologie   patologie   virologie   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• protilátky virové biosyntéza   MeSH
• represorové proteiny genetika   imunologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• virové plášťové proteiny genetika   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• HLA antigeny MeSH
• onkogenní proteiny virové MeSH
• protilátky virové MeSH
• represorové proteiny MeSH
• virové plášťové proteiny MeSH

BACKGROUND: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis. METHODS: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment. RESULTS: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients. CONCLUSIONS: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.

• Klíčová slova
• HPV, antibodies, follow-up, head and neck cancer, prognosis, survival,
• MeSH
• časové faktory MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• míra přežití MeSH
• nádory orofaryngu krev   mortalita   terapie   MeSH
• následné studie MeSH
• onkogenní proteiny virové imunologie   MeSH
• Papillomavirus E7 - proteiny imunologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• prospektivní studie MeSH
• protilátky virové krev   MeSH
• represorové proteiny imunologie   MeSH
• skvamocelulární nádory krev   mortalita   terapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• protilátky virové MeSH
• represorové proteiny MeSH

BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted. METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated. RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity. CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors. IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.

• MeSH
• dospělí MeSH
• ELISA MeSH
• infekce papilomavirem imunologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• mladý dospělý MeSH
• nádory orofaryngu imunologie   virologie   MeSH
• onkogenní proteiny virové imunologie   MeSH
• protilátky virové krev   MeSH
• represorové proteiny imunologie   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom imunologie   virologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• protilátky virové MeSH
• represorové proteiny MeSH

Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer.

• MeSH
• DNA virů analýza   genetika   MeSH
• dospělí MeSH
• infekce papilomavirem etiologie   genetika   virologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 11 imunologie   MeSH
• lidský papilomavirus 16 imunologie   MeSH
• lidský papilomavirus 18 imunologie   MeSH
• lidský papilomavirus 6 imunologie   MeSH
• nádorové proteiny biosyntéza   MeSH
• nádory plic komplikace   mortalita   virologie   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• Papillomaviridae genetika   MeSH
• prospektivní studie MeSH
• protilátky virové imunologie   MeSH
• retrospektivní studie MeSH
• RNA virová biosyntéza   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKN2A protein, human MeSH Prohlížeč
• DNA virů MeSH
• E6 protein, Human papillomavirus type 11 MeSH Prohlížeč
• E6 protein, Human papillomavirus type 31 MeSH Prohlížeč
• inhibitor p16 cyklin-dependentní kinasy MeSH
• nádorové proteiny MeSH
• onkogenní proteiny virové MeSH
• protilátky virové MeSH
• RNA virová MeSH

The purpose of this study was to determine whether changes in human papillomavirus (HPV) DNA prevalence in oral rinses and/or HPV-specific antibody levels in the sera of patients with oral/oropharyngeal cancer have prognostic significance. One hundred and forty-two patients with oral/oropharyngeal tumors were enrolled. The presence of HPV DNA was assayed in tumor tissue and oral rinses and HPV-specific antibodies were assessed in the sera. Oral rinses were collected before treatment and one year after the treatment. Sera were drawn before treatment, one month, and one year after the end of the treatment. Altogether, 59.2% of tumors were HPV positive. The presence of HPV DNA in the tumors correlated with HPV DNA positivity in oral rinses and with HPV-specific antibodies in the sera. Out of 66 patients with HPV-positive oral rinses at enrolment, 84.8% became negative at one-year follow-up, while most patients remained seropositive for HPV-specific antigens. However, the mean titers of HPV16 E6 and/or E7 antibodies at follow-up were significantly lower. Of 16 patients with recurrences at follow-up (alive on second sampling), six were positive at enrolment for HPV16 E6 and/or E7 antibodies. In five of these, no decrease in antibody levels was observed. Titers of antibodies specific for HPV16 capsid antigens did not change during the follow-up. Our data suggest that the detection of antibodies specific for the HPV 16 E6 and E7 oncoproteins may serve not only as a marker of HPV etiology, but also as a marker of recurrence and a prognostic indicator in patients with HPV-positive tumors.

• Klíčová slova
• HPV, antibodies, follow-up, head and neck cancer, oral rinses,
• MeSH
• DNA virů izolace a purifikace   MeSH
• infekce papilomavirem * krev   genetika   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• míra přežití MeSH
• nádorové biomarkery MeSH
• nádory hlavy a krku mortalita   virologie   MeSH
• onkogenní proteiny virové imunologie   MeSH
• Papillomavirus E7 - proteiny imunologie   MeSH
• prognóza MeSH
• protilátky virové krev   MeSH
• represorové proteiny imunologie   MeSH
• ústa virologie   MeSH
• virové plášťové proteiny imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA virů MeSH
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• nádorové biomarkery MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• protilátky virové MeSH
• represorové proteiny MeSH
• virové plášťové proteiny MeSH

Since its discovery, DNA vaccination has become an effective strategy for the development of vaccines against cancer including cervical carcinoma (CC). The formation of CC is associated with human papillomavirus (HPV) infection. Viral E6 and E7 oncoproteins are suitable targets for therapeutic vaccination. To adapt the HPV16 E6 oncogene for DNA immunisation, we performed several modifications. First we fused the E6 gene with the 5' or 3'-terminus of the Escherichia coli beta-glucuronidase (GUS) gene and showed enhanced immunogenicity of the 3' fusion (GUS.E6). Then, as the E6 oncogene contains two alternative introns that result in the production of truncated forms of the E6 protein, we abolished the 5' splice site in the E6 gene. This modification completely eliminated the expression of the truncated E6 transcripts and thus increased the production of the full-length E6 protein. At the same time, it moderately reduced the immunogenicity of the modified non-fused (E6cc) or fused (GUS.E6cc) genes, probably as a consequence of the substitution in the immunodominant E6 epitope following the abolishment of the splice site. Furthermore, we reduced the oncogenicity of the E6 protein by two point mutations (E6GT) that, together, prevented E6-mediated p53 degradation. Finally, we constructed the GUS.E6GT gene characterized by enhanced safety and immunogenicity when compared with the wild-type E6 gene.

• MeSH
• bodová mutace MeSH
• buněčné linie MeSH
• cytokiny biosyntéza   MeSH
• DNA vakcíny genetika   imunologie   MeSH
• exprese genu MeSH
• glukuronidasa genetika   imunologie   MeSH
• introny MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé MeSH
• lidský papilomavirus 16 genetika   imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory prevence a kontrola   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• proteiny z Escherichia coli genetika   imunologie   MeSH
• protilátky virové krev   MeSH
• rekombinantní fúzní proteiny genetika   imunologie   MeSH
• represorové proteiny genetika   imunologie   MeSH
• vakcíny proti papilomavirům genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• DNA vakcíny MeSH
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• glukuronidasa MeSH
• onkogenní proteiny virové MeSH
• proteiny z Escherichia coli MeSH
• protilátky virové MeSH
• rekombinantní fúzní proteiny MeSH
• represorové proteiny MeSH
• vakcíny proti papilomavirům MeSH

Tattooing has been shown to be very efficient at inducing immunity by vaccination with DNA vaccines. In this study, we examined the usability of tattooing for delivery of peptide vaccines. We compared tattooing with subcutaneous (s.c.) needle injection using peptides derived from human papillomavirus type 16 (HPV16) proteins. We observed that higher peptide-specific immune responses were elicited after vaccination with the simple peptides (E7(44-62) and E7(49-57)) and keyhole limpet hemocyanin-(KLH)-conjugated peptides (E7(49-57), L2(18-38) and L2(108-120)) with a tattoo device compared to s.c. inoculation. The administration of the synthetic oligonucleotide containing immunostimulatory CpG motifs (ODN1826) enhanced the immune responses developed after s.c. injection of some peptides (E7(44-62), KLH-conjugated L2(18-38) and L2(108-120)) to levels close to or even comparable to those after tattoo delivery of identical peptides with ODN1826. The highest efficacy of tattooing was observed in combination with ODN1826 for the vaccination with the less immunogenic E6(48-57) peptide and KLH-conjugated and non-conjugated E7(49-57) peptides which form the visible aggregates that could negatively influence the development of immune responses after s.c. injection but probably not after tattooing. In summary, we first evidenced that tattoo administration of peptide vaccines that might be useful in some cases efficiently induced both humoral and cell-mediated immune responses.

• MeSH
• cytotoxické T-lymfocyty imunologie   MeSH
• DNA vakcíny imunologie   MeSH
• hemokyanin imunologie   MeSH
• lidský papilomavirus 16 imunologie   MeSH
• molekulární sekvence - údaje MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• onkogenní proteiny virové imunologie   MeSH
• Papillomavirus E7 - proteiny MeSH
• peptidové fragmenty imunologie   MeSH
• represorové proteiny imunologie   MeSH
• sekvence aminokyselin MeSH
• tetování přístrojové vybavení   MeSH
• vakcinace * MeSH
• vakcíny proti papilomavirům imunologie   MeSH
• virové plášťové proteiny imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vakcíny MeSH
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• hemokyanin MeSH
• keyhole-limpet hemocyanin MeSH Prohlížeč
• L2 protein, Human papillomavirus type 16 MeSH Prohlížeč
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• peptidové fragmenty MeSH
• represorové proteiny MeSH
• vakcíny proti papilomavirům MeSH
• virové plášťové proteiny MeSH

The association between human papillomavirus (HPV) infection and the development of head and neck cancer has been documented recently. In this study on 86 head and neck cancer patients and 124 controls, data regarding demographics, behavioral risk factors, and risks related to HPV exposure were collected. HPV detection was carried out using polymerase chain reaction in the tumors and in oral exfoliated cells, and HPV typing by a reverse line blot assay specific for 37 HPV types. Sera were tested by an enzyme-linked immunosorbent assay specific for HPV proteins. Head and neck cancer cases report significantly more oral-anal contact (P = 0.02) and tobacco and alcohol use than controls (P = 0.001; P = 0.02, respectively). High-risk HPV DNA was detected in 43% of oral washings of cases and 4% of controls (P < 0.0001). The association between the presence of high-risk HPV DNA in oral exfoliated cells and in tumor tissues was statistically significant (adjusted P < 0.0001). The prevalence of HPV-specific antibodies was significantly higher in cases than in controls (adjusted P < 0.0001). These results provide epidemiological and immunological evidence for HR HPV as a strong risk factor (OR = 44.3, P < 0.0001) for head and neck cancer, even after controlling for age, tobacco and alcohol use. The detection of high-risk HPV DNA in oral exfoliated cells and HPV-specific antibodies in serum can be considered as clinically relevant surrogate markers for the presence of a HPV-associated head and neck cancer, with a high sensitivity (83%) and specificity (88%).

• MeSH
• demografie MeSH
• DNA virů analýza   genetika   MeSH
• hodnocení rizik MeSH
• infekce papilomavirem * epidemiologie   patologie   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• nádory hlavy a krku * epidemiologie   patologie   virologie   MeSH
• nádory orofaryngu virologie   MeSH
• onkogenní proteiny virové imunologie   MeSH
• Papillomaviridae genetika   imunologie   izolace a purifikace   MeSH
• Papillomavirus E7 - proteiny MeSH
• prevalence MeSH
• protilátky virové krev   MeSH
• represorové proteiny imunologie   MeSH
• rizikové faktory MeSH
• senzitivita a specificita MeSH
• sexuální chování MeSH
• specificita protilátek MeSH
• spinocelulární karcinom * epidemiologie   patologie   virologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DNA virů MeSH
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• protilátky virové MeSH
• represorové proteiny MeSH

Therapeutic DNA vaccines against oncogenic infection with human papillomavirus type 16 (HPV16) are mostly targeted against viral oncoproteins E7 and E6. To adapt the E7 oncoprotein for DNA immunization, we have previously reduced its oncogenicity by modification of the Rb-binding site and enhanced immunogenicity of the modified E7GGG gene by the fusion with the 5'-terminus of the gene encoding E. coli beta-glucuronidase (GUS). In this study, we attempted to improve immunogenicity of the GUS-based anti-E7 vaccines by increasing the steady-state level of fusion proteins. We fused deletion mutants of E7GGG and codon-optimized E7GGG with the 5'-terminus of GUS and unaltered E7GGG with the 3'-terminus of GUS. Furthermore, we mutated the initiation codon of the GUS gene in the E7GGG.GUS construct, as GUS alone was produced from this fusion gene. We found that only the fusion of E7GGG with the 3'-terminus of GUS (GUS.E7GGG) and deletion mutants of E7GGG with the 5'-terminus of GUS increased the steady-state level of fusion proteins in transfected human 293T cells. Analysis of immune reactions induced in mice by vaccination via a gene gun showed that the increased steady-state level of fusion proteins resulted in augmented production of E7-specific antibodies, but did not enhance cell-mediated anti-tumor immunity. Finally, we joined the signal sequence of the adenoviral E3 protein with GUS.E7GGG. This modification led to the predominant localization of the fusion protein in the endoplasmic reticulum and enhancement of CD8+ T-cell response, while antibody production was reduced. In conclusion, we found modifications of the E7GGG.GUS fusion gene that augmented either humoral or cell-mediated immune responses.

• MeSH
• buňky NIH 3T3 MeSH
• cytotoxické T-lymfocyty imunologie   MeSH
• DNA vakcíny imunologie   MeSH
• glukuronidasa genetika   imunologie   MeSH
• lidský papilomavirus 16 imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• Papillomavirus E7 - proteiny MeSH
• protilátky virové krev   MeSH
• rekombinantní fúzní proteiny imunologie   MeSH
• vakcíny proti papilomavirům imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vakcíny MeSH
• glukuronidasa MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• protilátky virové MeSH
• rekombinantní fúzní proteiny MeSH
• vakcíny proti papilomavirům MeSH

Therapeutic strategies based on the insertion of cytokine or other immunostimulatory genes into the genome of tumour cells followed by vaccination with the resulting, genetically modified, cytokine-producing vaccines represent a new potential prospect for the treatment of cancer patients. HPV 16 is the aetiological agent of more than 60 percent human cervical carcinomas (CC). At present, two prophylactic vaccines against HPV 16 are available (GlaxoSmithKline "Cervarix" and Merck "Gardasil"). These vaccines can almost completely protect the immunized individuals against both, persistent HPV 16 infection and HPV 16-related pathological findings in cervical cytology. In contrast, no clinically utilizable therapeutic vaccines against CC are available. During the last decade animal models have substantially contributed to the development of the therapeutic vaccines against HPV 16-associated tumours. It has been demonstrated that the HPV 16 E6/E7 oncoproteins can serve as tumour rejection antigens (TRA) and that the HPV 16-associated tumour cells can be genetically modified with DNA encoding immunostimulatory cytokines (IL-2, IL-12, GM-CSF) or other immunostimulatory molecules, used for vaccination, and inhibit tumour growth. To improve the HPV 16 antigen presentation in tumour-bearing individuals, dendritic cell-based vaccines loaded with HPV 16 E6/E7 DNA or hybrids of the dendritic and tumour cells have also been successfully employed. Unfortunately, when these encouraging approaches used in animal models were translated into clinical trials, the results were less optimistic. The problems that are still to be faced before the therapeutic vaccines against high-risk HPV-associated tumours can be approved for clinical purposes are discussed.

• MeSH
• cytokiny genetika   imunologie   MeSH
• infekce papilomavirem imunologie   prevence a kontrola   virologie   MeSH
• lidé MeSH
• lidský papilomavirus 16 genetika   imunologie   MeSH
• modely nemocí na zvířatech MeSH
• nádory děložního čípku imunologie   prevence a kontrola   virologie   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• Papillomavirus E7 - proteiny MeSH
• protinádorové vakcíny genetika   imunologie   MeSH
• racionální návrh léčiv MeSH
• rekombinantní kvadrivalentní vakcína proti lidskému papilomaviru typu 6, 11, 16, 18 MeSH
• represorové proteiny imunologie   MeSH
• vakcíny proti papilomavirům genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• human papillomavirus vaccine, L1 type 16, 18 MeSH Prohlížeč
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• protinádorové vakcíny MeSH
• rekombinantní kvadrivalentní vakcína proti lidskému papilomaviru typu 6, 11, 16, 18 MeSH
• represorové proteiny MeSH
• vakcíny proti papilomavirům MeSH