A high-risk papillomavirus 18 E7 affibody-enabled in vivo imaging and targeted therapy of cervical cancer

Wang, Ledan; Du, Wangqi; Zhu, Shanli; Jiang, Pengfei; Zhang, Lifang

doi:10.1007/s00253-019-09655-9

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…These affibodies quickly and specifically accumulated for clear, high-contrast tumor imaging within 2 h and were retained in tumors for over 8–12 h. In addition, similar to the observations of several previous studies ( Orlova et al, 2006 ; Xue et al, 2016 ; Jiang et al, 2018 ; Zhu J. et al, 2020 ; Zhu S. et al, 2020 ), Z HPV16E6 affibodies were also detectable in the kidneys. This could be explained by the passage of small proteins through the glomerular membrane, which is eventually absorbed by the proximal tubules ( Behr et al, 1998 ; Vegt et al, 2010 ; Wang et al, 2019 ). Also, the high affibody levels in the kidney could be attributed to the phenomenon that proteins less than 60 kDa are typically cleared by the renal ( Wang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…This could be explained by the passage of small proteins through the glomerular membrane, which is eventually absorbed by the proximal tubules ( Behr et al, 1998 ; Vegt et al, 2010 ; Wang et al, 2019 ). Also, the high affibody levels in the kidney could be attributed to the phenomenon that proteins less than 60 kDa are typically cleared by the renal ( Wang et al, 2019 ). Taken together, these characteristics strongly imply the favorability of Z HPV16E6 affibodies for molecular imaging and may improve the early diagnosis of HPV-related cancer for appropriate treatment choices.…”

Section: Discussionmentioning

confidence: 99%

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Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells

Zhu

Kamara

Wang

et al. 2021

Front. Cell Dev. Biol.

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Despite prophylactic vaccination campaigns, high-risk human papillomavirus (HPV)-induced cervical cancer remains a significant health threat among women, especially in developing countries. The initial occurrence and consequent progression of this cancer type primarily rely on, E6 and E7, two key viral oncogenes expressed constitutively, inducing carcinogenesis. Thus, E6/E7 have been proposed as ideal targets for HPV-related cancer diagnosis and treatment. In this study, three novel HPV16 E6-binding affibody molecules (ZHPV16E61115, ZHPV16E61171, and ZHPV16E61235) were isolated from a randomized phage display library and cloned for bacterial production. These affibody molecules showed high binding affinity and specificity for recombinant and native HPV16 E6 as determined by surface plasmon resonance, indirect immunofluorescence, immunohistochemistry, and near-infrared small animal optical imaging in vitro and in vivo. Moreover, by binding to HPV16 E6 protein, ZHPV16E61235 blocked E6-mediated p53 degradation, which increased the expression of some key p53 target genes, including BAX, PUMA and p21, and thereby selectively reduced the viability and proliferation of HPV16-positive cells. Importantly, ZHPV16E61235 was applied in combination with HPV16 E7-binding affibody ZHPV16E7384 to simultaneously target the HPV16 E6/E7 oncoproteins, and this combination inhibited cell proliferation more potently than either modality alone. Mechanistic studies revealed that the synergistic antiproliferative activity depends primarily on the induction of cell apoptosis and senescence but not cell cycle arrest. Our findings provide strong evidence that three novel HPV16 E6-binding affibody molecules could form a novel basis for the development of rational strategies for molecular imaging and targeted therapy in HPV16-positive preneoplastic and neoplastic lesions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells

Zhu

Kamara

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…To date, over 400 published studies show that affibody molecules have been selected for targeting more than 40 different proteins and served as affinity moieties in a variety of applications (Ståhl et al 2017). The affibody-targeted proteins include epidermal growth factor receptor (EGFR) (Andersson et al 2016;Oroujeni et al 2018), human epidermal growth factor receptor 2 (HER2) (Orlova et al 2006;Sörensen et al 2016), human epidermal growth factor receptor 3 (HER3) (Malm et al 2013;Schardt et al 2017), EBV LMP1 (Zhu et al 2020a) and LMP2 (Zhu et al2020b), and human papillomavirus type 16 E7 (HPV16E7) (Xue et al 2016;Zhu et al 2018) and HPV18E7 (Wang et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Generation of a novel affibody molecule targeting Chlamydia trachomatis MOMP

Shi

Jia

et al. 2021

Appl Microbiol Biotechnol

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Chlamydia trachomatis (C. trachomatis) is the leading cause of preventable blindness worldwide and the most prevalent cause of bacterial sexually transmitted diseases. At present, there is no available vaccine, and recurrences after antibiotics treatment are substantial problems. Major outer membrane protein (MOMP) accounts for 60% of the outer mass of C. trachomatis, functioning as trimeric porin, and it is highly antigenic. Therefore, MOMP is the most promising candidate for vaccine developing and target therapy of Chlamydia. Affibody, a new class of affinity ligands derived from the Z-domain in the binding region of Staphylococcus aureus protein A, has been the focus of researchers as a viable alternative to antibodies. In this study, the MOMP-targeted affibody molecule (ZMOMP:461) was screened by phage-displayed peptide library. Further, the affinity and specificity were characterized by surface plasmon resonance (SPR) and Western blot. Immunofluorescence assay (IFA) indicated that the MOMP-binding affibody could recognize native MOMP in HeLa229 cells infected C. trachomatis. Immunoprecipitation assay confirmed further that ZMOMP:461 molecule specifically recognizes the epitope on relaxed trimer MOMP. Our findings provide strong evidence that affibody molecule (ZMOMP:461) serves as substitute for MOMP antibody for biological applications and has a great potential for delivering drugs for target therapy. Key points • We screened a novel affibody molecule ZMOMP:461 targeting Chlamydia trachomatis MOMP. • ZMOMP:461 recognizes the recombinant and native MOMP with high affinity and specificity. • ZMOMP:461 could be internalized into live target cells.

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“…Further study by using whole animal imaging analysis indicated that a Z HPV18E7 affibody-targeted tumor tissue specifically appeared about 10 minutes after injection, and the affibody reached the highest level of tumor tissues 45 minutes after injection. At total of 24 hours after injection, the affibody still maintained a certain level in tumor tissues compared with other organs ( 43 ).…”

Section: Immunological Methods Based On Hpv Proteins For Diagnosismentioning

confidence: 99%

“…Interestingly, affibodies were also applied in HPV-positive tumors via targeting HPV oncoproteins. In a mouse cervical cancer model, Z HPV18E7 and Z HPV16E7 affibodies connected with Pseudomonas exotoxin, also known as affitoxins, were able to deliver Pseudomonas exotoxin, a clinically used anti-cancer agent to tumor tissues effectively, showing great potential for HPV-induced cancer treatment ( 43 , 111 ). These results exemplify the potential use of affitoxins for HPV-induced cancers.…”

Section: Therapeuticsmentioning

confidence: 99%

Immunodiagnosis and Immunotherapeutics Based on Human Papillomavirus for HPV-Induced Cancers

Dong

et al. 2021

Front. Immunol.

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Infection with human papillomavirus (HPV) is one of the main causes of malignant neoplasms, especially cervical, anogenital, and oropharyngeal cancers. Although we have developed preventive vaccines that can protect from HPV infection, there are still many new cases of HPV-related cancers worldwide. Early diagnosis and therapy are therefore important for the treatment of these diseases. As HPVs are the major contributors to these cancers, it is reasonable to develop reagents, kits, or devices to detect and eliminate HPVs for early diagnosis and therapeutics. Immunological methods are precise strategies that are promising for the accurate detection and blockade of HPVs. During the last decades, the mechanism of how HPVs induce neoplasms has been extensively elucidated, and several oncogenic HPV early proteins, including E5, E6, and E7, have been shown to be positively related to the oncogenesis and malignancy of HPV-induced cancers. These oncoproteins are promising biomarkers for diagnosis and as targets for the therapeutics of HPV-related cancers. Importantly, many specific monoclonal antibodies (mAbs), or newly designed antibody mimics, as well as new immunological kits, devices, and reagents have been developed for both the immunodiagnosis and immunotherapeutics of HPV-induced cancers. In the current review, we summarize the research progress in the immunodiagnosis and immunotherapeutics based on HPV for HPV-induced cancers. In particular, we depict the most promising serological methods for the detection of HPV infection and several therapeutical immunotherapeutics based on HPV, using immunological tools, including native mAbs, radio-labelled mAbs, affitoxins (affibody-linked toxins), intracellular single-chain antibodies (scFvs), nanobodies, therapeutical vaccines, and T-cell-based therapies. Our review aims to provide new clues for researchers to develop novel strategies and methods for the diagnosis and treatment of HPV-induced tumors.

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A high-risk papillomavirus 18 E7 affibody-enabled in vivo imaging and targeted therapy of cervical cancer

Cited by 10 publications

References 24 publications

Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells

Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells

Generation of a novel affibody molecule targeting Chlamydia trachomatis MOMP

Immunodiagnosis and Immunotherapeutics Based on Human Papillomavirus for HPV-Induced Cancers

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