Cervical cancer vaccines: Emerging concepts and developments

Silva, Diane M. Da; Eiben, Gretchen L.; Fausch, Steven C.; Wakabayashi, Mark T.; Rudolf, Michael P.; Velders, Markwin P.; Kast, W. Martin

doi:10.1002/1097-4652(200102)186:2<169::aid-jcp1023>3.0.co;2-h

Cited by 72 publications

(35 citation statements)

References 127 publications

(38 reference statements)

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“…Many prophylactic and therapeutic vaccine strategies are currently under development or in clinical trial. 3,4 The HPV16 oncoproteins E6 and E7, expressed in cervical carcinoma, are crucial for the development and the maintenance of the malignant phenotype. 1 These antigens are valuable targets for immunotherapy of tumors because they are able to elicit CTLmediated tumor rejection.…”

mentioning

confidence: 99%

Intracellular anti‐E7 human antibodies in single‐chain format inhibit proliferation of HPV16‐positive cervical carcinoma cells

Accardi

Donà

Bonito

et al. 2005

Intl Journal of Cancer

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The E7 tumor antigen of human papillomavirus type 16 (HPV16) is a validated target for immunodiagnosis and immunotherapy of HPV-associated cervical cancer. Anti-HPV16 E7 antibodies in scFv format were isolated from a human antibody phage display library and characterized. With the aim of interfering with the oncogenic activity of E7 protein, the most reactive of the selected antibody fragments was expressed by eukaryotic vectors in different compartments of the HPV16-positive cervical carcinoma SiHa cell line. The intracellular antibodies (intrabodies) were tested for their ability of inhibiting cell proliferation. A significant inhibition was obtained targeting the intrabodies to the nuclear and secretory compartments whereas no significant effect was observed in case of cytoplasmic localization. Inhibition was highly specific as no antiproliferative effect was obtained either with the E7-specific intrabodies in HPV-negative cells nor with irrelevant intrabodies in SiHa cells. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; E7 protein; intrabodies; singlechain variable fragment; antiproliferative effect; cervical cancer The HPV16 is involved in the aetiology of cervical cancer, the second main cause of cancer mortality in women worldwide.1,2 A real need exists to counter HPV infections either by prevention or by therapy. Many prophylactic and therapeutic vaccine strategies are currently under development or in clinical trial. 3,4The HPV16 oncoproteins E6 and E7, expressed in cervical carcinoma, are crucial for the development and the maintenance of the malignant phenotype.1 These antigens are valuable targets for immunotherapy of tumors because they are able to elicit CTLmediated tumor rejection.5 The HPV16 E7 has been shown recently to elicit antitumoral immunity in mice even when expressed in Nicotiana benthamiana plants. 6 This protein binds several tumour suppressors and promotes keratinocyte transformation by favoring DNA synthesis or inhibiting cellular differentiation.7-9 Several approaches have been explored to interfere with the HPV-induced abnormal proliferation by blocking the E7 activity at either gene or protein level, e.g., by phosphorothioate oligonucleotides, 10 short interfering RNA 11 and aptamers. 12 Intracellular immunization has provided new chances for interfering with the function of predetermined intracellular targets by directing antibodies in scFv format to specific compartments of mammalian cells. 13 The intracellular antibodies (intrabodies) can specifically recognize the target antigen in the intracellular environment and counteract its function with a not yet clarified mechanism of action, spanning from forming antigen-antibody complexes to diverting the target-antigen to unusual compartments.14 This approach has been employed already to achieve antineoplastic effects using intrabodies targeting oncogenic proteins.15 Evidence of antineoplastic effects was obtained in HPV16-positive human carcinoma cell lines by a hybridoma-derived recombinant scFv specific for the HPV16 E7...

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mentioning

confidence: 99%

Intracellular anti‐E7 human antibodies in single‐chain format inhibit proliferation of HPV16‐positive cervical carcinoma cells

Accardi

Donà

Bonito

et al. 2005

Intl Journal of Cancer

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“…O presente artigo de revisão explora os possíveis co-fatores do HPV na gênese do carcinoma escamoso do colo uterino, levando em conta apenas os fatores cuja associação com o vírus ou câncer cervical tenha sido documentada experimentalmente, e não apenas clínica ou epidemiologicamente. Dentre os 2,6,16,34,36,40,42,47,52,55 , bem como pelo esforço recente de pesquisadores no desenvolvimento de vacinas contra este vírus, com a finalidade de prevenção deste tipo de câncer 26,30,45,52 . A partir daí, esta revisão passa a explorar os possíveis co-fatores do HPV no processo de carcinogênese, levando em conta apenas os fatores cuja a associação com o vírus ou câncer cervical tenha sido documentada experimentalmente, e não apenas clínica ou epidemiologicamente.…”

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Co-fatores do HPV na oncogênese cervical

Pinto¹,

Túlio²,

Cruz³

2002

Rev. Assoc. Med. Bras.

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Artigo de RevisãoRESUMO O papilomavírus humano (HPV) exerce um papel central na carcinogênese do colo uterino. Em torno a ele orbitam outros fatores que influenciam direta ou indiretamente a instalação deste mecanismo no epitélio escamoso cervical. Investigações a respeito dos mecanismos de atuação e interação desses co-fatores com os elementos virais encontram-se na literatura dos últimos 20 anos. O presente artigo de revisão explora os possíveis co-fatores do HPV na gênese do carcinoma escamoso do colo uterino, levando em conta apenas os fatores cuja associação com o vírus ou câncer cervical tenha sido documentada experimentalmente, e não apenas clínica ou epidemiologicamente. Dentre os 2,6,16,34,36,40,42,47,52,55 , bem como pelo esforço recente de pesquisadores no desenvolvimento de vacinas contra este vírus, com a finalidade de prevenção deste tipo de câncer 26,30,45,52 . A partir daí, esta revisão passa a explorar os possíveis co-fatores do HPV no processo de carcinogênese, levando em conta apenas os fatores cuja a associação com o vírus ou câncer cervical tenha sido documentada experimentalmente, e não apenas clínica ou epidemiologicamente. Por não ser o objetivo desta revisão, fatores que têm sido vinculados ao HPV por estudos puramente epidemiológicos não serão abordados. Dentre eles incluem-se o início precoce da atividade sexual, multiplicidade de parceiros, baixa escolaridade e renda, multiparidade e história de doenças sexualmente transmissíveis 8 , incluindo infecção por clamídia 33,29 . O presente trabalho visa atualizar o leitor a respeito das certezas e incertezas da literatura acerca dos principais cofatores do HPV na gênese do carcinoma escamoso de colo uterino. Fatores imunológicosVários estudos na literatura suportam a forte associação existente entre a oncogênese e progressão neoplásica relacionada ao HPV e ao sistema imunológico. Entretanto, os mecanismos exatos que disparam o gatilho de uma resposta imune eficiente contra lesões relacionadas ao HPV ainda não são conhecidos. Eles podem estar relacionados à ativação do sistema imunológico ou à composição genética do hospedeiro.Uma vez que a exposição direta das oncoproteínas do HPV a células imunocompetentes não ocorre, é concebível que o desenvolvimento de anticorpos às proteínas virais possa depender de uma infecção secundária por meio de pequenas abrasões ou soluções de continuidade do epitélio, resultando na exposição das proteínas virais a estas células. No câncer relacionado ao HPV, este mecanismo depende da ocorrência de necrose celular do tecido proliferante invasor 18 . Resposta imune localA presença de células monomorfonucleares, principalmente células CD4 e ma-

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“…Viral antigens in tumors are known to be tumor specific antigens (eg HPV 16/18 E6 and E7 in cervical carcinoma) and serve as useful Leukemia targets for vaccination. 30 However, translocation products expressed in leukemia cells are also promising candidates as tumor antigens. Previous studies showed that leukemogenesisassociated fusion proteins, such as BCR/ABL 31,32 and PML/RAR␣, 33 have antigenicity and can act as leukemiaspecific antigens.…”

Section: Vaccination Against Tel/aml1 Positive Pre-b All Cellsmentioning

confidence: 99%

Prospects for immunotherapy of acute lymphoblastic leukemia

2001

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Acute lymphoblastic leukemia (ALL) is diagnosed in approximately 100 000 people worldwide per year and 70% of the patients are children. Most children have a good prognosis, as almost 80% will be cured, however only 30% of adults are cured. Additionally, the current chemotherapies have longlasting and severe side-effects. These findings indicate that the search for better and safer treatment modalities for ALL is still important. As leukemia directly affects the human immune cells, immunotherapeutic approaches have long been ignored as treatment options for this disease. However, increased knowledge of the immune system has opened new opportunities for immune modulation that could be of benefit to leukemia patients. Several recent advances towards immunotherapy of ALL will be discussed. Leukemia (2001) 15, 701-706.

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Cervical cancer vaccines: Emerging concepts and developments

Cited by 72 publications

References 127 publications

Intracellular anti‐E7 human antibodies in single‐chain format inhibit proliferation of HPV16‐positive cervical carcinoma cells

Intracellular anti‐E7 human antibodies in single‐chain format inhibit proliferation of HPV16‐positive cervical carcinoma cells

Co-fatores do HPV na oncogênese cervical

Prospects for immunotherapy of acute lymphoblastic leukemia

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