Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00604096" target="_blank" >RIV/61388971:_____/24:00604096 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216275:25310/24:39922262 RIV/00209805:_____/24:00080106

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1155/mi/9981131" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1155/mi/9981131</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1155/mi/9981131" target="_blank" >10.1155/mi/9981131</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF17_048%2F0007421" target="_blank" >EF17_048/0007421: Posilování mezioborové spolupráce ve výzkumu nanomateriálů a při studiu jejich účinků na živé organismy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Mediators of Inflammation

ISSN

0962-9351

e-ISSN

1466-1861

Svazek periodika

2024

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

9981131

Kód UT WoS článku

001385412900001

EID výsledku v databázi Scopus

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