All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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