Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I
Spontaneous tumor regression is a recognized phenomenon across various cancer types. Recent research emphasizes the alterations in autoantibodies against carbonic anhydrase I (CA I) (anti-CA I) levels as potential prognostic markers for various malignancies. Particularly, autoantibodies targeting CA...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/mi/9981131 |
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| author | Petra Chalova Barbora Jankovicova Veronika Dvorakova Eliska Zelinkova Zuzana Bilkova Marcela Slovakova Lucie Korecka Petr Muller Maksym Danchenko Lenka Minichova Jan Lakota Ludovit Skultety |
| author_facet | Petra Chalova Barbora Jankovicova Veronika Dvorakova Eliska Zelinkova Zuzana Bilkova Marcela Slovakova Lucie Korecka Petr Muller Maksym Danchenko Lenka Minichova Jan Lakota Ludovit Skultety |
| author_sort | Petra Chalova |
| collection | DOAJ |
| description | Spontaneous tumor regression is a recognized phenomenon across various cancer types. Recent research emphasizes the alterations in autoantibodies against carbonic anhydrase I (CA I) (anti-CA I) levels as potential prognostic markers for various malignancies. Particularly, autoantibodies targeting CA I and II appear to induce cellular damage by inhibiting their respective protein’s catalytic functions. Our study illuminates the profound impact of anti-CA I autoantibodies from patient serum on the esterase activity of human CA I, exhibiting inhibitory effects akin to the acetazolamide inhibitor. Concurrently, our newly synthesized mouse monoclonal IgG antibody, mAb 2B8, against human CA I showcased a potent inhibitory action. An in-depth exploration into mAb 2B8′s binding dynamics with its target enzyme was undertaken. Leveraging epitope extraction and phage display library techniques, we identified the amino acid sequence DFWTYP (positions 191–196 of CA I) as crucial for mAb 2B8′s interaction. In 3-D structural analysis, this sequence is spatially adjacent to a previously identified epitope (DFWTYP) that interacts with patient-derived autoantibodies. Critically, mAb 2B8 demonstrated an ability to infiltrate eukaryotic cells, engaging specifically with its intracytoplasmic target. This positions mAb 2B8 as a promising model for future studies aimed at tumor cell eradication. |
| format | Article |
| id | doaj-art-03ceba87db344d8e88e4780caa6c892a |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-03ceba87db344d8e88e4780caa6c892a2025-01-07T00:00:03ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/mi/9981131Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase IPetra Chalova0Barbora Jankovicova1Veronika Dvorakova2Eliska Zelinkova3Zuzana Bilkova4Marcela Slovakova5Lucie Korecka6Petr Muller7Maksym Danchenko8Lenka Minichova9Jan Lakota10Ludovit Skultety11Biomedical Research CenterDepartment of Biological and Biochemical SciencesDepartment of Biological and Biochemical SciencesDepartment of Biological and Biochemical SciencesDepartment of Biological and Biochemical SciencesDepartment of Biological and Biochemical SciencesDepartment of Biological and Biochemical SciencesRegional Centre for Applied Molecular OncologyInstitute of ChemistryBiomedical Research CenterInstitute of Normal and Pathological PhysiologyBiomedical Research CenterSpontaneous tumor regression is a recognized phenomenon across various cancer types. Recent research emphasizes the alterations in autoantibodies against carbonic anhydrase I (CA I) (anti-CA I) levels as potential prognostic markers for various malignancies. Particularly, autoantibodies targeting CA I and II appear to induce cellular damage by inhibiting their respective protein’s catalytic functions. Our study illuminates the profound impact of anti-CA I autoantibodies from patient serum on the esterase activity of human CA I, exhibiting inhibitory effects akin to the acetazolamide inhibitor. Concurrently, our newly synthesized mouse monoclonal IgG antibody, mAb 2B8, against human CA I showcased a potent inhibitory action. An in-depth exploration into mAb 2B8′s binding dynamics with its target enzyme was undertaken. Leveraging epitope extraction and phage display library techniques, we identified the amino acid sequence DFWTYP (positions 191–196 of CA I) as crucial for mAb 2B8′s interaction. In 3-D structural analysis, this sequence is spatially adjacent to a previously identified epitope (DFWTYP) that interacts with patient-derived autoantibodies. Critically, mAb 2B8 demonstrated an ability to infiltrate eukaryotic cells, engaging specifically with its intracytoplasmic target. This positions mAb 2B8 as a promising model for future studies aimed at tumor cell eradication.http://dx.doi.org/10.1155/mi/9981131 |
| spellingShingle | Petra Chalova Barbora Jankovicova Veronika Dvorakova Eliska Zelinkova Zuzana Bilkova Marcela Slovakova Lucie Korecka Petr Muller Maksym Danchenko Lenka Minichova Jan Lakota Ludovit Skultety Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I Mediators of Inflammation |
| title | Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I |
| title_full | Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I |
| title_fullStr | Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I |
| title_full_unstemmed | Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I |
| title_short | Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I |
| title_sort | inhibitory effect of human anti ca i autoantibodies and development of monoclonal antibody mab 2b8 targeting carbonic anhydrase i |
| url | http://dx.doi.org/10.1155/mi/9981131 |
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