Conjugation of HPV16 E7 to cholera toxin enhances the HPV-specific T-cell recall responses to pulsed dendritic cells in vitro in women with cervical dysplasia

Nurkkala, Merja; Wassén, Lotta; Nordström, Inger; Gustavsson, Inger; Slavica, Lucija; Josefsson, Agnetha; Eriksson, Kristina

doi:10.1016/j.vaccine.2010.06.068

Cited by 13 publications

(8 citation statements)

References 52 publications

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“…Therefore, it is important to study the HPV58 E6 and E7 HLA-A2-restricted CTL epitope peptide in Chinese population. At present, some HLA-A2 (+) CTL epitopes in HPV16 E7 protein, such as E7 [11][12][13][14][15][16][17][18][19] and E7 49-57, have been identified and accepted (18)(19)(20). At present, many studies have confirmed the effectiveness of these epitopes as antigen targets (21)(22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, researchers have found that the cytotoxic T lymphocyte (CTL) epitope of the HPV16 E6 and E7 oncoproteins match human leukocyte antigen (HLA)-A2, which is currently considered the most common human major histocompatibility complex (MHC)-I molecule; the immunogenicity of these epitope has been confirmed using transgenic mice (11). In vitro, lymphocytes from human peripheral blood previously immunized with the HPV16 polypeptide vaccine induced specific CTL immune responses and killed HPV16-positive tumor cells (12,13). However, the CTL epitope for HPV58 has not been found.…”

Section: Introductionmentioning

confidence: 99%

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Prediction and identification of human leukocyte antigen‑A2‑restricted cytotoxic T lymphocyte epitope peptides from the human papillomavirus 58 E7 protein

Wang

Chen

et al. 2018

Oncol Lett

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Persistent infection with high-risk human papilloma virus (HPV) is the primary cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. HPV58 is the third most common HPV genotype in China after HPV16 and HPV18. HPV E6 and E7 are oncoproteins and are constitutively expressed in HPV-associated cancer cells, therefore they are considered to be ideal target antigens for immunotherapy, including HPV therapeutic vaccine. In the present study, human leukocyte antigen (HLA)-A2-restricted cytotoxic T lymphocyte (CTL) epitope peptides were predicted and screened from HPV58 E7 antigen and their immunogenicity was subsequently determined. A total of 6 HLA-A2-binding peptides derived from HPV58 E7 were predicted and selected using 3 different prediction programs. A negative control peptide and PBS were used as two negative controls. Peripheral blood mononuclear cells (PBMCs) with HLA-A2(+) allele were used to detect the specific cellular immune response among the 6 predicted peptides by enzyme-linked immunospot assay (ELISOPT). Following preliminary screening for the predicted peptides, the antigenicity of the peptide HPV58 E7 was further assessed by an immunoassay to a vaccine contained HPV58 E7 antigen. Specific humoral and cellular immunity were detected using the peptide HPV58 E7 as the specific antigen. A total of 6 peptides from HPV58 E7 protein were predicted and subsequently named P1 (E7: TLREYILDL), P2 (E7: DLHPEPTDL), P3 (E7: CINSTTTDV), and P4 (E7: STTTDVRTL), P5 (E7: TLQQLLMGT) and P6 (E7: LLMGTCTIV). In the ELISPOT assay on HLA-A2 (+) human PBMCs, interferon (IFN)-γ-production was evident in the P2 and P4 groups. The average numbers of IFN-γ associated spots in the P2 and P4 groups was 50.61±5.37 spot-forming cells (SFC)/1×10 and 266±34.42 SFC/1×10, respectively. The numbers of spots in the two peptides were significantly increased compared with the other 4 peptides and the control groups (P<0.05). In the further antigenicity verification of P4 (HPV58 E7), the peptide only stimulated the humoral immune response of the AD-HPV16/18/58 mE6E7 vaccine containing HPV58 E7 antigen. Compared with the 2 negative control groups (1:400), the antibody titers of the vaccine group (1:25,600) were significantly increased (P<0.05). In cellular immunoassays the average number of IFN-γ associated spots was 143.3±32.13 SFC/1×10 in the vaccine group, which was significantly enhanced compared with the PBS group (8±5.29 SFC/1×10; P<0.01) and the AD-NC group (28±5.13 SFC/1×10; P<0.01). The peptide HPV58 E7 (STTTDVRTL) displayed sufficient antigenicity to a vaccine contained HPV58 E7 antigen. Therefore, HPV58 E7 peptide may be considered as a candidate epitope peptide for the construction of HPV58 peptide vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prediction and identification of human leukocyte antigen‑A2‑restricted cytotoxic T lymphocyte epitope peptides from the human papillomavirus 58 E7 protein

Wang

Chen

et al. 2018

Oncol Lett

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“…Representative examples of antigens delivered with CT include tetanus toxoid Xu-Amano et al, 1994;Marinaro et al, 1995), Helicobacter pylori urease (Saldinger et al, 1998;Pappo et al, 1995), pneumococcal polysaccharide or surface proteins (Yamamoto et al, 1997a;Vancott et al, 1996), Haemophilus influenzae lipooligosaccharide (Hong et al, 2010), inactivated influenza virus (Bergmann and Waldman, 1988), Candida albicans (De Bernardis et al, 2002), and Eh29 antigen from Entameba histolytica (Carrero et al, 2010). CT-adjuvanted vaccines potentiate antigen-specific S-IgA, serum IgG, IgM, IgE, and cellular responses (Bourguin et al, 1991;Xu-Amano et al, 1993;Tanaka et al, 2007;Hodge et al, 2001;Nurkkala et al, 2010;Vendetti et al, 2009). The molecular events and immunological actions presumed to induce these responses are described later in this chapter.…”

Section: Cholera Toxinmentioning

confidence: 99%

Mucosal Adjuvants

Freytag

Clements

2015

Mucosal Immunology

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“…However, the specific mechanism of chemotherapy drug resistance remains unclear. Nurkkala et al (15) demonstrated that inhibition of phosphatase and tensin homolog (PTEN)-targeted regulation by an AKT inhibitor or miR-214 directly could reduce the miR-214-mediated survival rate and cisplatin-resistance through PTEN/AKT signaling in PTEN/AKT-induced ovarian cancer drug-resistant cells. The above methods could increase chemotherapy drug sensitivity of ovarian cancer patients, which could be used in the treatment of recurrent and chemotherapy-resistant ovarian cancer in order to improve the treatment of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

Liu

et al. 2016

Oncology Letters

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Abstract. The present study aimed to explore the expression of microRNA (miRNA or miR) in drug-resistant and drug-sensitive ovarian cancer cell lines, and to seek the potential therapeutic target of ovarian cancer drug-resistant mechanism in order to improve drug resistance by altering miRNA levels. The drug-resistant characteristics of SKOV3/DDP, SKOV3, COC1/DDP and COC1 cell lines were studied. The miRNAs that were differentially expressed between cisplatin-resistant cells and its parental cells in ovarian cancer were screened with a miRNA chip. The effect of miRNAs was detected, and their drug-resistant mechanism was investigated by transfection and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods. Among the expression screening of miRNAs, 41 mRNAs, including Homo sapiens (hsa)-miR-30a-5p and hsa-miR-34c-5p, were highly expressed in the drug-resistant cells, whereas 44 miRNAs, including hsa-miR-96-5p and hsa-miR-200c-3p, were lowly expressed. The expression levels of hsa-miR-30a-5p in two types of ovarian cancer chemotherapy-resistant cell lines were significantly higher than those in chemotherapy-sensitive cell lines, which was associated with ovarian cancer chemotherapy resistance. In conclusion, high expression of miRNA-30a-5p was able to promote cell growth and colony forming ability, and enhance cell migration and invasion. Thus, miRNA-30a-5p is expected to become a meaningful novel target for ovarian cancer resistant treatment.

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Conjugation of HPV16 E7 to cholera toxin enhances the HPV-specific T-cell recall responses to pulsed dendritic cells in vitro in women with cervical dysplasia

Cited by 13 publications

References 52 publications

Prediction and identification of human leukocyte antigen‑A2‑restricted cytotoxic T lymphocyte epitope peptides from the human papillomavirus 58 E7 protein

Prediction and identification of human leukocyte antigen‑A2‑restricted cytotoxic T lymphocyte epitope peptides from the human papillomavirus 58 E7 protein

Mucosal Adjuvants

Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

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