Characterization of HLA-A2-restricted HPV-16 E7-specific CD8+ T-cell immune responses induced by DNA vaccines in HLA-A2 transgenic mice

Peng, Shiwen; Trimble, Cornelia L.; He, Liangmei; Tsai, Ya Chea; Lin, Cheng Tao; Boyd, David A.; Pardoll, Drew M.; Hung, Chien Fu; Wu, T. C.

doi:10.1038/sj.gt.3302607

Cited by 45 publications

(70 citation statements)

References 22 publications

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“…We observed that the presence of the E7 49-57 aa sequence within the E7 gene of the CRT/E7 DNA vaccine suppresses the efficient activation of HLA-A2 restricted E7 (aa [11][12][13][14][15][16][17][18][19][20] peptide-specific CD8 + T cell-mediated immune responses 13 in HLA-A2 transgenic mice. In order to avoid this situation and accurately characterize the HLA-A2-restricted E7-specific CD8 + T-cell immune response in HLA-A2 transgenic mice, we generated pcDNA3-CRT/ mtE7(del aa49-57), a DNA vaccine that deletes aa49-57 from the E7 gene.…”

Section: Combination Of Hpv E6 and E7 Dna Vaccines S Peng Et Almentioning

confidence: 99%

“…We found that vaccination with pcDNA3-CRT/E7(del aa49-57) generates HLA-A2-restricted E7 (aa11-20) peptide-specific CD8 + T-cell immune response in HLA-A2 transgenic mice. 13 In the current study, we characterized the HLA-A2-restricted E6-and/or E7-specific CD8 + T-cell immune responses generated by vaccination with pcDNA3-CRT/ E6 and/or pcDNA3-CRT/mtE7(del aa49-57) in HLA-A2 transgenic mice by intracellular cytokine staining followed by flow cytometry analysis. As shown in Figure 4, vaccination with pcDNA3-CRT/E6 and pcDNA3-CRT/ mtE7(del aa49-57) generated comparable numbers of HLA-A2-restricted E6 (aa29-38)-specific CD8 + T cells to vaccination with pcDNA3-CRT/E6 without pcDNA3-CRT/mtE7(del aa49-57).…”

Section: Combination Of Hpv E6 and E7 Dna Vaccines S Peng Et Almentioning

confidence: 99%

“…12 We have recently employed HLA-A2 (AAD) transgenic mice to characterize immune responses to E7 DNA vaccines. 13 As HLA-A2 transgenic mice also express murine MHC class I molecules (H-2D b and K b ), when HLA-A2 transgenic mice were vaccinated with DNA encoding CRT linked to wild-type E7, the vaccinated mice generated predominantly H-2D b -restricted E7-specific CD8…”

Section: Combination Of Hpv E6 and E7 Dna Vaccines S Peng Et Almentioning

confidence: 99%

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A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

et al. 2005

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Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancers. HPV E6 and E7 are two viral oncoproteins that are consistently expressed in HPV infections and HPVassociated malignancies. We have previously developed DNA vaccines encoding calreticulin (CRT) linked either to HPV type 16 (HPV-16) E6 or to HPV-16 E7, both of which generated significant antitumor effects against E6-and E7-expressing tumors. In this study, we demonstrate that simultaneous vaccination of C57BL/6 mice or HLA-A2 transgenic mice with both CRT/E6 and CRT/E7 DNA vaccines generates significant E6-and E7-specific T-cell immune responses in vaccinated mice. Furthermore, combined vaccination with both CRT/E6 and CRT/E7 DNA generates significantly better therapeutic antitumor effects against HPV E6-and E7-expressing tumors than vaccination with either CRT/E6 DNA or CRT/E7 DNA alone. Our data suggest that it may be desirable to combine DNA vaccines targeting E6 with DNA vaccines targeting E7 to develop effective immunotherapeutic strategies for control of HPV infection and HPV-associated lesions in a clinical setting.

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Section: Combination Of Hpv E6 and E7 Dna Vaccines S Peng Et Almentioning

confidence: 99%

Section: Combination Of Hpv E6 and E7 Dna Vaccines S Peng Et Almentioning

confidence: 99%

Section: Combination Of Hpv E6 and E7 Dna Vaccines S Peng Et Almentioning

confidence: 99%

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A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

et al. 2005

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“…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). However, to date, there have been limited data on HPV 18 therapeutic vaccines.…”

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

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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.

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“…The TC1/A2 line was generated by transforming TC1 cells with HLA-A*0201 from HLA-A*0201 (AAD) transgenic mice. 60 The limitation of this line is that the CD81 T-cell immune response is predominantly directed to against the H-2Db-restricted HPV16 E7 (49-57) epitope in HLA-A*0201 (AAD) transgenic mice. The HLF16 line was generated by transfecting heart lung fibroblasts from HLA-A*0201 transgenic mice with the HPV16 E6 and E7 oncogenes and H-Ras V12.…”

Section: Murine Modelsmentioning

confidence: 99%

Recent advances in strategies for immunotherapy of human papillomavirus‐induced lesions

Kanodia

Silva

Kast

2007

Intl Journal of Cancer

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Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for ''proof of concept'' studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in preclinical models for HPVinduced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; immunotherapy; therapeutic vaccines; immunomodulation; animal models; clinical trialsThe human papillomaviruses (HPVs) are a family of sexually transmitted, double-stranded DNA viruses with over 100 different genotypes identified till date. HPV genotypes are divided into the low-risk and high-risk categories based on the spectrum of lesions they induce. Fifteen HPV types are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82); 3 are classified as probable high-risk types (26, 53 and 66) and 12 are classified as low-risk types (6,11,40,42,43,44,54,61,70,72, 81 and CP6108). 1 The low-risk types primarily induce benign genital condylomas and low-grade squamous intraepithelial lesions whereas the high-risk types are most frequently associated with the development of anogenital cancers and can be detected in 99% of cervical cancers, 2 with HPV16 found in about 50% of cases. 3 Infection by the low-risk types is not confined to the anogenital area and can cause other diseases such as recurrent respiratory papillomatosis. Similarly, infection by the high-risk types is also not confined to the anogenital area, since 18.3% of cancers of the oropharynx contain DNA from these types. 4 In the United States, an estimated 75% of the sexually active general population ages 15-49 years acquires at least one genital HPV type during their lifetime. 5 Though most individuals remain asymptomatic and spontaneously clear their infections, a small percentage of patients develop clinically or histologically recognizable lesions that develop into invasive cancer. The widespread use of cervical cytological screening using Papanicolaou (Pap) smear tests has reduced the mortality rate from cervical cancer in developed countries. However, in developing countries where screening programs are minimal, cervical cancer remains the second leading cause of cancer-related deaths among women. 6 Furthermore, Pap smear tests will not help identify HPV infection in males, where it can cause penile and anal cancers as well as cancers of the head and neck. Thus, it is essential to develop effective prophylactic and therapeutic strategies directed against HPV. Prophylactic vaccinesWhile therapeutic vaccines aim to develop a strong ...

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Characterization of HLA-A2-restricted HPV-16 E7-specific CD8+ T-cell immune responses induced by DNA vaccines in HLA-A2 transgenic mice

Cited by 45 publications

References 22 publications

A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

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

Recent advances in strategies for immunotherapy of human papillomavirus‐induced lesions

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