6XXO

Crystal structure of NB8, a nanobody targeting prostate specific membrane antigen

Summary for 6XXO

• Entry DOI: 10.2210/pdb6xxo/pdb
• Descriptor: NB_8 (2 entities in total)
• Functional Keywords: nanobody, prostate-specific membrane antigen, antibody drug conjugate, cancer imaging, anti-cancer drugs., antitumor protein
• Biological source: Camelus dromedarius (Arabian camel)
• Total number of polymer chains: 1
• Total formula weight: 15714.06

Authors

Shahar, A.,Rosenfeld, L.,Papo, N. (deposition date: 2020-01-28, release date: 2020-06-10, Last modification date: 2024-11-13)

Primary citation

Rosenfeld, L.,Sananes, A.,Zur, Y.,Cohen, S.,Dhara, K.,Gelkop, S.,Ben Zeev, E.,Shahar, A.,Lobel, L.,Akabayov, B.,Arbely, E.,Papo, N.
Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer.
J.Med.Chem., 63:7601-7615, 2020

PubMed Abstract: The repertoire of methods for the detection and chemotherapeutic treatment of prostate cancer (PCa) is currently limited. Prostate-specific membrane antigen (PSMA) is overexpressed in PCa tumors and can be exploited for both imaging and drug delivery. We developed and characterized four nanobodies that present tight and specific binding and internalization into PSMA cells and that accumulate specifically in PSMA tumors. We then conjugated one of these nanobodies to the cytotoxic drug doxorubicin, and we show that the conjugate internalizes specifically into PSMA cells, where the drug is released and induces cytotoxic activity. studies show that the extent of tumor growth inhibition is similar when mice are treated with commercial doxorubicin and with a 42-fold lower amount of the nanobody-conjugated doxorubicin, attesting to the efficacy of the conjugated drug. These data highlight nanobodies as promising agents for the imaging of PCa tumors and for the targeted delivery of chemotherapeutic drugs.

PubMed: 32442375
DOI: 10.1021/acs.jmedchem.0c00418

Experimental method

X-RAY DIFFRACTION (1.5 Å)