Targeting Prostate Cancer Using Bispecific T-Cell Engagers against Prostate-Specific Membrane Antigen
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F23%3A00578734" target="_blank" >RIV/86652036:_____/23:00578734 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/23:10473389
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsptsci.3c00159" target="_blank" >https://pubs.acs.org/doi/10.1021/acsptsci.3c00159</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsptsci.3c00159" target="_blank" >10.1021/acsptsci.3c00159</a>
Alternative languages
Result language
angličtina
Original language name
Targeting Prostate Cancer Using Bispecific T-Cell Engagers against Prostate-Specific Membrane Antigen
Original language description
Prostate cancer (PCa) tops the list of cancer-related deaths in men worldwide. Prostate-specific membrane antigen (PSMA) is currently the most prominent PCa biomarker, as its expression levels are robustly enhanced in advanced stages of PCa. As such, PSMA targeting is highly efficient in PCa imaging as well as therapy. For the latter, PSMA-positive tumors can be targeted directly by using small molecules or macromolecules with cytotoxic payloads or indirectly by engaging the immune system of the host. Here we describe the engineering, expression, purification, and biological characterization of bispecific T-cell engagers (BiTEs) that enable targeting PSMA-positive tumor cells by host T lymphocytes. To this end, we designed the 5D3-alpha CD3 BiTE as a fusion of single-chain fragments of PSMA-specific 5D3 and anti-CD3 antibodies. Detailed characterization of BiTE was performed by a combination of size-exclusion chromatography, differential scanning fluorimetry, and flow cytometry. Expressed in insect cells, BiTE was purified in monodisperse form and retained thermal stability of both functional parts and nanomolar affinity to respective antigens. 5D3-alpha CD3's efficiency and specificity were further evaluated in vitro using PCa-derived cell lines together with peripheral blood mononuclear cells isolated from human blood. Our data revealed that T-cells engaged via 5D3-alpha CD3 can efficiently eliminate tumor cells already at an 8 pM BiTE concentration in a highly specific manner. Overall, the data presented here demonstrate that the 5D3-alpha CD3 BiTE is a candidate molecule of high potential for further development of immuno-therapeutic modalities for PCa treatment.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
ISSN
2575-9108
e-ISSN
2575-9108
Volume of the periodical
6
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
1703-1714
UT code for WoS article
001082649700001
EID of the result in the Scopus database
2-s2.0-85176088907