更新于：2024-11-01

HSPA1A x HPV E7

更新于：2024-11-01

基本信息

关联

项与 HSPA1A x HPV E7 相关的药物

HPV 16 E7/HSP70 fused DNA vaccine(The Johns Hopkins University)

靶点

HPV E7 x HSPA1A

作用机制

E7调节剂 [+1]

在研机构

The Johns Hopkins University

原研机构

The Johns Hopkins University

在研适应症

卵巢癌 [+2]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HSPA1A x HPV E7 相关的临床结果

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100 项与 HSPA1A x HPV E7 相关的转化医学

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0 项与 HSPA1A x HPV E7 相关的专利（医药）

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项与 HSPA1A x HPV E7 相关的文献（医药）

2018-04-01·Archives of Pharmacal Research3区 · 医学

Use of protein-based biomarkers of exfoliated cervical cells for primary screening of cervical cancer

3区 · 医学

Article

作者: Kim, Yun Hwan ; Kim, Hyoung Jin ; Kim, Hong-Jin ; Ju, Woong ; Kim, Seung Cheol ; Jin, Yingji

There has been no attempt to apply protein-based markers of exfoliated cervical cells (ECCs) for primary screening of cervical cancer. In the present study, the levels of six tumor-associated protein [TAPs: Sialyl Lewis A (SLeA), Cancer Antigen 15-3 (CA 15-3), p53, heat shock protein (Hsp)70, Hsp27 and squamous cervical carcinoma antigen (SCCA)]and of two human papillomavirus (HPV) viral proteins (HPV16 E7 and HPV16 L1) of ECCs lysates were evaluated by enzyme-linked immunosorbent assays (ELISAs).The wells of 96-well plates were coated with the ECCs lysates from normal, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cancer groups, and candidate proteins were detected by relevant antibodies. SLeA level decreased with increasing severity of lesions, whereas the levels of other candidate proteins increased. SLeA, HPV16 L1 and p53 levels appeared more useful for detecting cervical lesions than the other candidates. The combination of ELISA-SLeA and ELISA-HPV16 L1 could efficiently detect cervical lesions from normal. The combination of ELISA-SLeA and ELISA-p53 could powerfully discriminate cancer from normal with 91.3% sensitivity and 96.7% specificity. The protein levels of ECCs have great potential as biomarkers for primary screening of cervical cancer.

2011-07-15·International Journal of Cancer1区 · 医学

Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7

1区 · 医学

Article

作者: Ton N. Schumacher ; Mireille Toebes ; Raquel Gomez ; Joost H. van den Berg ; John B. Haanen ; Koen Oosterhuis ; Peter Öhlschläger

AbstractTo allow vaccination irrespective of HLA type, DNA vaccines encoding full‐length antigens are required. However, here, we demonstrate that the immunogenicity of DNA vaccines encoding the full‐length human papillomavirus (HPV) type 16 E7 and E6 proteins is highly reduced compared to vaccines encoding only the immunodominant epitope. Furthermore, the low remaining immunogenicity is essentially lost for both E7 and E6 when a nononcogenic “gene‐shuffled” variant is utilized. To address these issues, we tested whether alterations in transgene design can restore the immunogenicity of full‐length and gene‐shuffled DNA vaccines. Remarkably, genetic fusion of E7 with tetanus toxin fragment C (TTFC) resulted in a dramatic increase in immunogenicity both for the full‐length and the gene‐shuffled version of E7. Moreover, the TTFC fusion vaccines were more immunogenic than a vaccine encoding a fusion of E7 and mycobacterial heat shock protein‐70, which has recently been tested in a clinical trial. Interestingly, vaccination with these TTFC fusion vaccines also resulted in extremely persistent T‐cell responses. The E7‐specific CD8+ T cells induced by TTFC fusion vaccines were functional in terms of IFN‐γ production, formation of immunological memory, in vivo cytolytic activity and tumor eradication. Finally, we show that genetic fusion with TTFC also improves the immunogenicity of a gene‐shuffled E6 DNA vaccine. These data demonstrate that genetic fusion with tetanus toxin fragment C can dramatically improve the immunogenicity of full‐length and gene‐shuffled DNA vaccines. The DNA fusion vaccines developed here will be evaluated for the treatment of HPV‐positive carcinomas in future studies.

2005-06-01·The Journal of Gene Medicine4区 · 医学

Combined immunization with fusion genes of mutated E7 gene of human papillomavirus type 16 did not enhance antitumor effect

4区 · 医学

Article

作者: Martina Dusková ; Jana Macková ; Michal Smahel ; Viera Ludvíková ; Simon Rittich ; Dana Pokorná

AbstractBackgroundThe E7 oncoprotein of human papillomavirus type 16 (HPV16) is frequently used as a model tumor‐associated antigen. Its immunogenicity has been substantially enhanced by fusion with several proteins of various origins and functions. Different mechanisms have been responsible for increased vaccination efficacy of fusion proteins.Methods and resultsWe linked E7 and its mutated form (E7GGG) with the mouse heat‐shock protein 70.1 (HSP70.1). Enhanced immunogenicity of both fusion genes administered via a gene gun was demonstrated by protection of C57BL/6 mice against oncogenic MHC class I positive TC‐1 cells producing the HPV16 E7 oncoprotein but not against the MHC class I negative TC‐1/A9 subline. To assess if the efficacy of E7‐based DNA vaccines could be increased by combination of various fusion genes, we combined the HSP70.1 fusion genes (i.e. E7HSP or E7GGGHSP) with the fusion construct linking E7GGG with targeting signals of lysosome‐associated membrane protein 1 (Sig/E7GGG/LAMP‐1). Treatment of mice 4 days after TC‐1 cell inoculation showed moderately higher immunization potency of HSP70.1 fusion genes in comparison with the Sig/E7GGG/LAMP‐1 gene. Any combination of two fusion genes given in the same gene gun shot neither was more effective compared with single genes nor protected mice against TC‐1/A9 cells. As fusion of E7GGG with E. coli glucuronidase (E7GGG.GUS) had been previously proven to provide partial protection from TC‐1/A9‐induced tumors, we also combined E7GGGHSP with E7GGG.GUS. The genes were inoculated either in mix in two gene gun shots or separately each gene in one shot into opposite sides of the abdomen. Neither mode of combined immunization induced higher protection than E7GGG.GUS alone. However, doubling the DNA dose considerably enhanced the antitumor efficacy of E7GGG.GUS.ConclusionsWe constructed highly immunogenic fusions of HPV16 E7 and E7GGG with mouse HSP70.1. Furthermore, we substantially enhanced protection against TC‐1/A9 cells with downregulated MHC class I expression by doubling the pBSC/E7GGG.GUS dose, but we failed to demonstrate a beneficial effect of any combination of two fusion genes with different mechanisms causing enhancement of HPV16 E7 immunogenicity. Copyright © 2005 John Wiley & Sons, Ltd.