The αvβ6 integrin specific virotherapy, Ad5_NULL-A20.FCU1, selectively delivers potent "in-tumour" chemotherapy to pancreatic ductal adenocarcinoma.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) represent an unmet clinical need. Approximately 90% of PDACs express high levels of αvβ6 integrin. We have previously described Ad5_NULL-A20, an adenovirus vector with ablated native means of cell entry and retargeted to αvβ6 integrin by incorporation of an A20 peptide.

Methods

Here, we incorporate suicide genes FCY1 and FCU1 encoding for cytosine deaminase (CDase) or a combination of CDase and UPRTase, capable of catalysing a non-toxic prodrug, 5-FC into the chemotherapeutic 5-FU and downstream metabolites, into replication-deficient Ad5 and Ad5_NULL-A20.

Results

We show that Ad5_NULL-A20 enables the transfer of suicide genes to αvβ6 integrin-positive PDAC cells which, in combination wit

SUBMITTER: Badder LM 

PROVIDER: S-EPMC11555051 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature