In addition, Nectin-4 represents a potential target in TNBC, and its role in molecular defined breast cancer subtype should be investigated in larger patient cohorts.
In vitro, this ADC bound to nectin-4 with high affinity and specificity and induced its internalisation as well as dose-dependent cytotoxicity on nectin-4-expressing breast cancer cell lines.
The ADAM (<u>a</u><u>d</u>isintegrin <u>a</u>nd <u>m</u>etalloproteinase) proteases are involved in ectodomain cleavage of transmembrane proteins, and ADAM17 is known to cleave Nectin-4 in breast cancer.
Increased levels of PVRL4 protein were observed in cell membrane, cytoplasm and nuclei of glioblastoma, breast and ovarian tumor clinical samples with no significant change in PVRL4 mRNA levels in glioblastoma and breast cancer compared with their corresponding control samples, suggesting that PVRL4 is likely post-transcriptionally regulated.
We showed that, unlike the MV vaccine strains, rMV-SLAMblind used PVRL4 (polio virus receptor-related 4) as a receptor to infect breast cancer cells and not the ubiquitously expressed CD46.
In vivo, Nectin-4 is re-expressed in breast carcinoma, and a circulating form of Nectin-4 is detected in the sera of patients with metastatic breast cancer.