Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs
Human Papillomavirus 16-associated cancer, affecting primarily the uterine cervix but, increasingly, other body districts, including the head–neck area, will long be a public health problem, despite there being a vaccine. Since the virus oncogenic activity is fully ascribed to the viral E6 and E7 on...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1803 |
| _version_ | 1797563264216858624 |
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| author | Carla Amici Maria Gabriella Donà Barbara Chirullo Paola Di Bonito Luisa Accardi |
| author_facet | Carla Amici Maria Gabriella Donà Barbara Chirullo Paola Di Bonito Luisa Accardi |
| author_sort | Carla Amici |
| collection | DOAJ |
| description | Human Papillomavirus 16-associated cancer, affecting primarily the uterine cervix but, increasingly, other body districts, including the head–neck area, will long be a public health problem, despite there being a vaccine. Since the virus oncogenic activity is fully ascribed to the viral E6 and E7 oncoproteins, one of the therapeutic approaches for HPV16 cancer is based on specific antibodies in single-chain format targeting the E6/E7 activity. We analyzed the Complementarity Determining Regions, repositories of antigen-binding activity, of four anti-HPV16 E6 and -HPV16 E7 scFvs, to highlight possible conformity to biophysical properties, recognized to be advantageous for therapeutic use. By epitope mapping, using E7 mutants with amino acid deletions or variations, we investigated differences among the anti-16E7 scFvs in terms of antigen-binding capacity. We also performed computational analyses to determine whether length, total net charge, surface hydrophobicity, polarity and charge distribution conformed well to those of the antibodies that had already reached clinical use, through the application of developability guidelines derived from recent literature on clinical-stage antibodies, and the Therapeutic Antibodies Profiler software. Overall, our findings show that the scFvs investigated may represent valid candidates to be developed as therapeutic molecules for clinical use, and highlight characteristics that could be improved by molecular engineering. |
| first_indexed | 2024-03-10T18:40:10Z |
| format | Article |
| id | doaj.art-ffc86efa14c14ddfb5ff0dbf708275e4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:40:10Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ffc86efa14c14ddfb5ff0dbf708275e42023-11-20T05:55:59ZengMDPI AGCancers2072-66942020-07-01127180310.3390/cancers12071803Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor DrugsCarla Amici0Maria Gabriella Donà1Barbara Chirullo2Paola Di Bonito3Luisa Accardi4Department of Biology, University of Rome Tor Vergata, 00133 Rome, ItalySTI/HIV Unit, Istituto Dermatologico San Gallicano IRCCS, 00144 Rome, ItalyDepartment of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, ItalyHuman Papillomavirus 16-associated cancer, affecting primarily the uterine cervix but, increasingly, other body districts, including the head–neck area, will long be a public health problem, despite there being a vaccine. Since the virus oncogenic activity is fully ascribed to the viral E6 and E7 oncoproteins, one of the therapeutic approaches for HPV16 cancer is based on specific antibodies in single-chain format targeting the E6/E7 activity. We analyzed the Complementarity Determining Regions, repositories of antigen-binding activity, of four anti-HPV16 E6 and -HPV16 E7 scFvs, to highlight possible conformity to biophysical properties, recognized to be advantageous for therapeutic use. By epitope mapping, using E7 mutants with amino acid deletions or variations, we investigated differences among the anti-16E7 scFvs in terms of antigen-binding capacity. We also performed computational analyses to determine whether length, total net charge, surface hydrophobicity, polarity and charge distribution conformed well to those of the antibodies that had already reached clinical use, through the application of developability guidelines derived from recent literature on clinical-stage antibodies, and the Therapeutic Antibodies Profiler software. Overall, our findings show that the scFvs investigated may represent valid candidates to be developed as therapeutic molecules for clinical use, and highlight characteristics that could be improved by molecular engineering.https://www.mdpi.com/2072-6694/12/7/1803therapeutic antibodiessingle-chain antibody fragmentsHPV-associated cancerclinical stage antibodiesHuman Papillomavirus 16 E6 and E7 oncoproteins |
| spellingShingle | Carla Amici Maria Gabriella Donà Barbara Chirullo Paola Di Bonito Luisa Accardi Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs Cancers therapeutic antibodies single-chain antibody fragments HPV-associated cancer clinical stage antibodies Human Papillomavirus 16 E6 and E7 oncoproteins |
| title | Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs |
| title_full | Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs |
| title_fullStr | Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs |
| title_full_unstemmed | Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs |
| title_short | Epitope Mapping and Computational Analysis of Anti-HPV16 E6 and E7 Antibodies in Single-Chain Format for Clinical Development as Antitumor Drugs |
| title_sort | epitope mapping and computational analysis of anti hpv16 e6 and e7 antibodies in single chain format for clinical development as antitumor drugs |
| topic | therapeutic antibodies single-chain antibody fragments HPV-associated cancer clinical stage antibodies Human Papillomavirus 16 E6 and E7 oncoproteins |
| url | https://www.mdpi.com/2072-6694/12/7/1803 |
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