OUR RESEARCH
COMPANY HIGHLIGHTS
Viral protein-derived peptide drug inhibits cancer cell growth by targeting MYC oncogene expression. MYC is driving cancer growth approximately 70% of all different types of cancers. By delivering the small peptide to specific cell types with a form of antibody-drug conjugate, we increase the efficacies of both existing and developing antibody drugs.
What does make this drug different from others?
The peptide is designed based on the viral protein sequence. Viruses likely originated millions of years ago, and viruses have evolutionally developed strategies to hijack host cell functions. When a herpesvirus is replicating in a cell, cell growth stops. We isolated the functional protein domain, which is responsible for the virus taking over RNA synthesis machinery. Even cancer cells, cannot escape from being targeted by viruses.
With the strategy, we made “undruggable” a “druggable” with viral power, which holds significant potential as a cancer drug and also other disease treatments, because MYC is an essential molecule for robust cell growth.
How does the drug work?
Decoy for cell transcription activator
Cellular protein needs to flexibly interact with enzymes through a domain called the transactivation domain. Many transcription regulators share the activator complex though relatively weak interactions, which allow for the local transcription factors to interact with enzymes in a concentration-dependent manner. If one transcription factor dominates resources, other transcription factors cannot activate their target genes when necessary. Viral transcription factor? They need to take as much as they can for their own gene transcription to complete replication in a short time; this makes viral peptides potent inhibitors for host cell protein complex formations.
Targeting Myc transcription
The peptide isolated from a viral activator efficiently binds to cellular enzymes that are necessary for MYC to work. Viral protein has better efficacy to take the enzyme for its own replication. We isolated and modified a small protein domain, which is critical for the function.
How effective?
Cancer cell growth inhibition in vitro
Multiple lymphoma and leukemia cell lines were incubated with VGN50 in tissue culture. Cell growth was measured with color metric assays. Incubation with VGN50 prevents cancer cell growth. Normal primary blood mononuclear cells were approximately 10x less sensitive for the VGN50 treatment because they are not as active as cancer cells.
Inhibition of primary effusion lymphoma growth in a xenograft model
Cancer cell growth inhibition over toxicity to mice was examined by the xenograft mouse model. VGN50 inhibited primary effusion lymphoma (PEL) without showing toxicity to the mice (left). PEL is one of the most aggressive types of B-cell lymphoma cells. Ascites fluid produced by cancer cells and the number of PEL in the body cavity is also reduced by VGN50 treatment. Isolated cancer cells also demonstrated cell atrophy, a characteristic of MYC inhibition (Shimoda et al., Communs Biol 2021).
ADVANTAGES OVER CURRENT METHODS
Better Efficacies
Viral protein is continuously evolving to regulate host cell functions for their own replication. It has naturally acquired better efficacies from necessity.
Small molecule peptide
The small size of the peptide allows conveniently attached to multiple ligands. The small sizes and specificity also make great candidates as a payload for antibody-drug conjugates for targeting.
Modular design
By changing targeting ligands, peptides can be delivered to specific cell types, where attenuation of highly active MYC activity is desirable.