University of Pittsburgh

Oncolytic Viruses Targeting STAT3

This oncolytic vaccinia virus employs precise genetic engineering to produce high levels of a STAT3 inhibitor within tumor sites. By inserting a nucleic acid sequence coding for either the full-length PIAS3 protein or its functional fragment—sometimes fused to a membrane translocation sequence—this technology ensures selective viral replication in cancer cells while sparing normal tissue. The targeted expression from a specific locus, such as the thymidine kinase gene, enables robust localized inhibitor production and a bystander effect through associated cell-penetrating peptides, thereby enhancing the overall STAT3 suppression in the tumor microenvironment.

Description

This technology stands out by integrating the targeted lytic action of an oncolytic virus with molecularly precise inhibition of a key cancer-promoting pathway. Its design facilitates high local concentrations of the inhibitor, overcoming challenges associated with systemic administration and toxicity. Unlike traditional therapeutic approaches, the virus’s selective replication and enhanced gene expression not only increase efficacy but also reduce off-target effects, offering a promising advancement in cancer treatment modalities.

Applications

Cancer oncolytic therapy
STAT3 targeted therapy
Combination cancer treatment
Viral vector manufacturing

Advantages

Selective replication in tumor cells minimizes damage to healthy tissues while maximizing local STAT3 inhibition.
High-level, localized production of STAT3 inhibitors reduces systemic off-target toxicities.
Cell-penetrating peptides enable a bystander effect, amplifying the therapeutic impact against surrounding cancer cells.
Enhanced viral replication within the tumor microenvironment boosts overall antitumor efficacy.
Complementary use with standard cancer therapies increases treatment versatility and potential synergistic effects.

IP Status

https://patents.google.com/patent/US11253559B2