Targeting prostate cancer by new bispecific monocyte engager directed to prostate-specific membrane antigen

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00618581" target="_blank" >RIV/86652036:_____/25:00618581 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/25:10502174

Result on the web

<a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0307353" target="_blank" >https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0307353</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0307353" target="_blank" >10.1371/journal.pone.0307353</a>

Result language

angličtina

Original language name

Targeting prostate cancer by new bispecific monocyte engager directed to prostate-specific membrane antigen

Original language description

Prostate cancer (PCa) ranks as the second leading cause of cancer-related deaths among men in the United States. Prostate-specific membrane antigen (PSMA) represents a well-established biomarker of PCa, and its levels correlate positively with the disease progression, culminating at the stage of metastatic castration-resistant prostate cancer. Due to its tissue-specific expression and cell surface localization, PSMA shows superior potential for precise imaging and therapy of PCa. Antibody-based immunotherapy targeting PSMA offers the promise of selectively engaging the host immune system with minimal off-target effects. Here we report on the design, expression, purification, and characterization of a bispecific engager, termed 5D3-CP33, that efficiently recruits macrophages to the vicinity of PSMA-positive cancer cells mediating PCa death. The engager was engineered by fusing the anti-PSMA 5D3 antibody fragment to a cyclic peptide 33 (CP33), selectively binding the Fc gamma receptor I (Fc gamma RI/CD64) on the surface of phagocytes. Functional parts of the 5D3-CP33 engager revealed a nanomolar affinity for PSMA and Fc gamma RI/CD64 with dissociation constants of KD = 3 nM and KD = 140 nM, respectively. At a concentration as low as 0.3 nM, the engager was found to trigger the production of reactive oxygen species by U937 monocytic cells in the presence of PSMA-positive cells. Moreover, flow cytometry analysis demonstrated antibody-dependent cell-mediated phagocytosis of PSMA-positive cancer cells by U937 monocytes when exposed to 0.15 nM 5D3-CP33. Our findings illustrate that 5D3-CP33 effectively and specifically activates monocytes upon PSMA-positive target engagement, resulting in the elimination of tumor cells. The 5D3-CP33 engager can thus serve as a promising lead for developing new immunotherapy tools for the efficient treatment of PCa.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30102 - Immunology

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

Publication year

2025

Confidentiality

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

Name of the periodical

PLoS ONE

ISSN

1932-6203

e-ISSN

1932-6203

Volume of the periodical

20

Issue of the periodical within the volume

3

Country of publishing house

US - UNITED STATES

Number of pages

19

Pages from-to

e0307353

UT code for WoS article

001448306400032

EID of the result in the Scopus database

2-s2.0-105000284683