Interleukin‐12‐secreting human papillomavirus type 16–transformed cells provide a potent cancer vaccine that generates E7‐directed immunity

Hallez, Sophie; Detremmerie, Odile; Giannouli, Christina; Thielemans, Kris; Gajewski, Thomas F.; Burny, Arsène; Léo, Oberdan

doi:10.1002/(sici)1097-0215(19990505)81:3<428::aid-ijc17>3.0.co;2-#

Cited by 45 publications

(22 citation statements)

References 28 publications

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“…Transduction of tumor cells with genes encoding costimulatory molecules or cytokines may enhance immunogenicity, leading to T-cell activation and antitumor effects after vaccination. 162 Vaccines using HPV-transformed tumor cells transduced with cytokine genes, such as interleukin-12, 163 interleukin-2, 164 or GM-CSF, 165 can generate strong antitumor effects in mice.…”

Section: Tumor Cell-based Vaccinesmentioning

confidence: 99%

Vaccination to prevent and treat cervical cancer

2004

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Section: Tumor Cell-based Vaccinesmentioning

confidence: 99%

Vaccination to prevent and treat cervical cancer

2004

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“…Several HPV-related tumor-cell-based vaccines have been reported in pre-clinical model systems. For example, vaccines involving HPV-transformed tumor cells transduced with cytokine genes such as IL-12 (Hallez et al, 1999) and IL-2 (Bubenik et al, 1999) have been demonstrated to generate strong anti-tumor effects in mice. Recently, it has been shown that an E7-expressing GM-CSF gene-transduced allogeneic tumor-cell-based vaccine can generate E7-specific CTL activities and protective anti-tumor immunity in immunized mice .…”

Section: (371) Dendritic Cell-based Vaccinesmentioning

confidence: 99%

Development of HPV Vaccines for HPV-associated Head and Neck Squamous Cell Carcinoma

Devaraj

Gillison

2003

Critical Reviews in Oral Biology & Medicine

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High-risk genotypes of the human papillomavirus (HPV), particularly HPV type 16, are found in a distinct subset of head and neck squamous cell carcinomas (HNSCC). Thus, these HPV-associated HNSCC may be prevented or treated by vaccines designed to induce appropriate HPV virus-specific immune responses. Infection by HPV may be prevented by neutralizing antibodies specific for the viral capsid proteins. In clinical trials, vaccines comprised of HPV virus-like particles (VLPs) have shown great promise as prophylactic HPV vaccines. However, given that capsid proteins are not expressed at detectable levels by infected basal keratinocytes, vaccines with therapeutic potential must target other non-structural viral antigens. Two HPV oncogenic proteins, E6 and E7, are important in the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing carcinomas. Therefore, therapeutic vaccines targeting these proteins may have potential to control HPV-associated malignancies. Various candidate therapeutic HPV vaccines are currently being tested whereby E6 and/or E7 is administered in live vectors, in peptides or protein, in nucleic acid form, as components of chimeric VLPs, or in cell-based vaccines. Encouraging results from experimental vaccination systems in animal models have led to several prophylactic and therapeutic vaccine clinical trials. Should they fulfill their promise, these vaccines may prevent HPV infection or control its potentially life-threatening consequences in humans.

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“…The importance of costimulatory molecules like CD80 is undisputed in the induction of effective anti-tumor immune responses (58,59). Furthermore, a potent anti-tumor effect of IL-12 has been described, either by systemically administered IL-12 (60) or by vaccination with poorly immunogenic tumor cells transfected with IL-12 genes (29,61). Furthermore, synergistic effects of expression of CD80 simultaneously with the secretion of IL-12 in inducing protective immunity against poorly immunogenic tumors in vivo have been demonstrated (62,63).…”

Section: Induction Of Epitope-specific T Cell Responses By Dcs Loadedmentioning

confidence: 99%

Human Dendritic Cells Are Activated by Chimeric Human Papillomavirus Type-16 Virus-Like Particles and Induce Epitope-Specific Human T Cell Responses In Vitro

Rudolf

Fausch

Silva

et al. 2001

The Journal of Immunology

134

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Human papillomavirus (HPV)-derived chimeric virus-like particles (VLPs) are the leading candidate vaccine for the treatment or prevention of cervical cancer in humans. Dendritic cells (DCs) are the most potent inducers of immune responses and here we show for the first time evidence for binding of chimeric HPV-16 VLPs to human peripheral blood-derived DCs. Incubation of immature human DCs with VLPs for 48 h induced a significant up-regulation of the CD80 and CD83 molecules as well as secretion of IL-12. Confocal microscopy analysis revealed that cell surface-bound chimeric VLPs were taken up by DCs. Moreover, DCs loaded with chimeric HPV-16 L1L2-E7 VLPs induced an HLA-*0201-restricted human T cell response in vitro specific for E7-derived peptides. These results clearly demonstrate that immature human DCs are fully activated by chimeric HPV-16 VLPs and subsequently are capable of inducing endogenously processed epitope-specific human T cell responses in vitro. Overall, these findings could explain the high immunogenicity and efficiency of VLPs as vaccines.

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Interleukin‐12‐secreting human papillomavirus type 16–transformed cells provide a potent cancer vaccine that generates E7‐directed immunity

Cited by 45 publications

References 28 publications

Vaccination to prevent and treat cervical cancer

Vaccination to prevent and treat cervical cancer

Development of HPV Vaccines for HPV-associated Head and Neck Squamous Cell Carcinoma

Human Dendritic Cells Are Activated by Chimeric Human Papillomavirus Type-16 Virus-Like Particles and Induce Epitope-Specific Human T Cell Responses In Vitro

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