Cancer can exploit immune regulatory checkpoints molecules by inhibiting anti-tumor immune responses from T cells. These immune checkpoint inhibitor (ICI) antibodies that activate anti-tumor immune responses can create durable responses in 10%–20% of cancer patients, but the remaining 80%–90% of the patients do not respond, driving the need to find novel combination therapies that increase the number of responders to ICI therapies.
Researchers from the University of Helsinki developed a platform enveloping oncolytic viruses with peptides to activate and direct T cells to respond to a tumor. The oncolytic viruses, already in clinical use, are naturally occurring viruses that have been modified to specifically kill cancer cells either by direct cell lysis or by inducing a strong anti-viral immune response against the virus and the host cells. A major weakness of current oncolytic viruses is that a strong anti-viral immune response does not necessarily correlate to a strong anti-tumor immune response.
Peptide-coated oncolytic-enveloped viruses, or simply PeptiENV, train the patient’s own, locally active T cells to identify tumor cells with the patient’s own cancer peptides. Researchers attached tumor-specific peptides onto the viral envelope of either the vaccinia virus or herpes simplex virus 1 (HSV-1), using a cell-penetrating peptide sequence derived from human immunodeficiency virus Tat protein. Cell-penetrating peptides typically function to facilitate intake/uptake of molecular cargo through endocytosis and researchers proposed to use their membrane penetrating properties to be repurposed as an anchor. Alternatively, the therapeutic peptides could be conjugated with cholesterol for the attachment of the peptides onto the viral envelope. The PeptiENV platform was tested using mouse melanoma models resulted in a positive increase in tumor infiltration by T cells.
Personalized cancer therapies are highly sought after, and the PeptiENV platform is capable of adapting to changes in the hosts’ tumor antigens by simply coating the virus with new tumor specific antigens, allowing the immune response to properly react. This provides an opportunity to generate personalized cancer vaccines by customizing viral-coated peptide sequences.
The article titled “Personalized Cancer Vaccine Platform for Clinically Relevant Oncolytic Enveloped Viruses” was published in Molecular Therapy.