The cell-mediated immune response to human papillomavirus-induced cervical cancer: Implications for immunotherapy

Eiben, Gretchen L.; Velders, Markwin P.; Kast, W. Martin

doi:10.1016/s0065-230x(02)86004-3

Cited by 28 publications

(27 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These genes are also required for the maintenance of transformed phenotype. As a consequence, E6 and E7 are ideal immunotherapeutic targets to induce cellular immune responses against HPVtransformed cells (6,7). Significant efforts have been made to develop HPV 16 therapeutic vaccines that target either E6 or E7 proteins (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

Yan

Harris

Khan³

et al. 2008

Vaccine

View full text Add to dashboard Cite

Human papilloma-virus (HPV) infection is the major cause of cervical cancer. HPV 18 is the most prevalence high-risk HPV after type 16 that accounts for the largest number of cervical cancer cases worldwide. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines for targeting tumors post infection. In this study, we utilize a novel multi-phase strategy for HPV 18 antigen development with the goal of increasing anti-HPV18 cellular immunity. Our data show that this construct can induce strong cellular immune responses against HPV 18 E6 and E7 antigens in a murine model. Moreover, when applied to Rhesus monkeys, this construct is also able to elicit cellular immunity. These data suggest such DNA immunogens are candidates for further study in the eventual context of immunotherapy for HPV-associated cancers.

show abstract

mentioning

confidence: 99%

Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

Yan

Harris

Khan³

et al. 2008

Vaccine

View full text Add to dashboard Cite

show abstract

“…As a consequence, E6 and E7 are potential targets for immunotherapeutic intervention strategies involving induction or stimulation of cytotoxic T lymphocyte (CTL) activity against HPV-transformed cells. 3 It is likely that HPV-specific CTLs play an important role in the immunological control of tumor development after HPV infection. 3 Indeed, while the majority of sexually active women become infected with HPV, only a minority develops premalignant cervical lesions or cervical cancer.…”

mentioning

confidence: 99%

“…3 It is likely that HPV-specific CTLs play an important role in the immunological control of tumor development after HPV infection. 3 Indeed, while the majority of sexually active women become infected with HPV, only a minority develops premalignant cervical lesions or cervical cancer. 4 In these patients, as expected, HPVspecific CTL activity is generally low, 5,6 suggesting that they have mounted a certain degree of immunological tolerance or ignorance for the HPV-derived antigens.…”

mentioning

confidence: 99%

Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mice

Riezebos‐Brilman

Regts

et al. 2005

Gene Ther

View full text Add to dashboard Cite

Despite promising preclinical results of various therapeutic anticancer immunization strategies, these approaches may not be effective enough to eradicate tumors in cancer patients. While most animal models are based on fastgrowing transplantable tumors, malignancies in, for example, cervical cancer patients in general develop much more slowly, which may lead to immune suppression and/or immune tolerance. As a consequence, the immunomodulating signal of any therapeutic immunization regimen should be sufficiently potent to overcome this immunocompromised condition. In previous studies, we demonstrated that an experimental vaccine against human papillomavirus (HPV)-induced cervical cancer, based on Semliki Forest virus (SFV), induces robust HPV-specific cellular immune responses in mice. Now we studied whether this strategy is potent enough to also prime a cellular immune response in immune-tolerant HPV transgenic mice, in which CTL activity cannot be induced using protein or DNA vaccines. We demonstrate that, depending on the route of immunization, SFV-expressing HPV16 E6 and E7 indeed has the capacity to induce HPV16 E7-specific cytotoxic T cells in HPVtransgenic mice. Gene Therapy (2005) Cervical cancer is the third most common cancer among women worldwide. It is caused by infection with highrisk human papillomavirus (HPV), in particular types 16, 18, 31, 33 or 45. Indeed, in over 99% of all cervical carcinomas, DNA derived from these HPV types is detectable. 1 High-risk HPVs have the capacity to transform cervical epithelial cells by integrating the open reading frames encoding the viral early proteins E6 and E7 into the host cell genome. This integration may lead to constitutive overexpression of E6 and E7, mediating transformation of the cells to a malignant phenotype. 2 Since the continued production of E6 and E7 is required for the maintenance of the transformed phenotype, E6 and E7 in fact represent tumor-specific antigens in cervical carcinoma and premalignant HPV-transformed cells. As a consequence, E6 and E7 are potential targets for immunotherapeutic intervention strategies involving induction or stimulation of cytotoxic T lymphocyte (CTL) activity against HPV-transformed cells. 3

show abstract

“…2010. 40: 3075-3084 DOI 10.1002 Immunity to infection 3075 prevalence and persistence of HPV infections in immunosuppressed individuals [4] and by the fact that an increased cellular immune response is correlated with a good clinical prognosis [5]. The DC lineage is a family of professional APC.…”

Section: Introductionmentioning

confidence: 99%

“…Additional environmental and/or host factors are probably involved in malignant progression as suggested by the small proportion of infected individuals developing cervical cancer and the relatively long latency period before cancer emergence [3]. The importance of the immune system in the control of HPV infection and lesion development is shown, indirectly, by the high prevalence and persistence of HPV infections in immunosuppressed individuals [4] and by the fact that an increased cellular immune response is correlated with a good clinical prognosis [5].…”

Section: Introductionmentioning

confidence: 99%

The L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context

Herman¹,

Hubert²,

Herfs³

et al. 2010

Eur J Immunol

View full text Add to dashboard Cite

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. The aim of this study was to determine whether HPV16 viral particles can influence the trafficking of human DC/ Langerhans cells (LC), either by direct interactions with DC or following incubation with human normal keratinocytes that are in close contact with LC in the squamous epithelium. We first demonstrated that HPV16 L1 major capsid protein, when self-assembled into virus-like particles (VLP), is able to induce in DC an over-expression of CXC receptor 4 (CXCR4) via the activation of the NF-jB signaling pathway and to enhance DC motility in the presence of CXCL12, suggesting an ability to migrate towards lymph nodes. We also showed that conditioned media of HPV16 VLP-treated keratinocytes induce a lower LC migration than those from untreated keratinocytes and that prostaglandin E2 (PGE 2 ), detected in HPV16 VLP-treated keratinocyte supernatants, may reduce LC recruitment into the squamous epithelium. Taken together, our data demonstrate that HPV16 VLP may differentially regulate the immune protective response according to their target cells.Key words: APC . Cell trafficking . Chemokines . HPV16 VLP Supporting Information available online IntroductionMore than 90% of cervical cancers and precursor lesions (squamous intraepithelial lesions, SIL) may be attributed to the infection by oncogenic types of human papillomavirus (HPV) [1]. However, HPV alone is not sufficient for tumor progression [2]. Additional environmental and/or host factors are probably involved in malignant progression as suggested by the small proportion of infected individuals developing cervical cancer and the relatively long latency period before cancer emergence [3]. The importance of the immune system in the control of HPV infection and lesion development is shown, indirectly, by the high Eur. J. Immunol. 2010. 40: 3075-3084 DOI 10.1002 Immunity to infection 3075 prevalence and persistence of HPV infections in immunosuppressed individuals [4] and by the fact that an increased cellular immune response is correlated with a good clinical prognosis [5]. The DC lineage is a family of professional APC. On exposure to danger signals such as pathogens, immature DC are able to process antigens and to mature through a dramatic change in their cell surface markers [6]. The migration of maturing DC to the draining lymph nodes results in the interactions between DC and naive T cells and in the initiation of an antigen-specific immune response [7]. Furthermore, the signals induced within draining lymph nodes can cause the expansion of lymphatic vessels, sustaining and amplifying the effective homing of DC [8]. Indeed, migration of DC from the site of antigen capture to secondary lymphoid organs is a crucial event in the initiation and amplification of immune responses. In turn, inflammatory sites can recruit circulating...

show abstract

The cell-mediated immune response to human papillomavirus-induced cervical cancer: Implications for immunotherapy

Cited by 28 publications

References 143 publications

Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mice

The L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context

Contact Info

Product

Resources

About