Promega, Madison, Wis, has entered into a global collaboration with Merck, Kenilworth, NJ, to develop Promega’s microsatellite instability (MSI) technology as an on-label, solid tumor companion diagnostic for use with Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab). The companies will initially seek regulatory approval for the Promega MSI companion diagnostic in the United States and China, but may follow with plans to seek approvals in additional territories.

The Promega technology is a PCR-based method for detecting MSI, a form of genomic instability caused by the insertion or deletion of additional bases into DNA microsatellites—that is, regions of repeating bases distributed throughout the human genome. During DNA replication, failure of the mismatch repair system to correct such errors causes MSI.

MSI status is a measure of deficient mismatch repair found in certain solid tumors, providing oncologists, pathologists, and patients with information that characterizes tumors and can guide care and treatment. The current Promega research use only MSI assay has been available and used in the market since 2004.

“It is gratifying to see our MSI technology have such meaning within the oncology community,” says Bill Linton, president and CEO of Promega. “Promega developed this technology well over a decade ago, and our long-term commitment to research and development helped evolve its use.”

Promega MSI technology has been validated in labs around the world to characterize solid tumor MSI status. MSI testing functionally measures the genomic accumulation of insertion or deletion (indel) errors caused by a deficient mismatch-repair system that occurs in certain types of solid tumors. Such screening may be used to better characterize tumors and guide therapeutic choices for MSI-high cancer types.

Promega MSI (1)Tumors with MSI-high status have been shown to respond to immune checkpoint inhibitor therapies. This outcome may be explained by MSI-driven tumor expression of mutation-associated neoantigens, which are believed to cause immune cell infiltration into the tumor microenvironment. Tumor-induced inhibition of immune cell activity can be overcome with immune checkpoint inhibitor therapies, allowing immune cells to destroy the tumor cells.

“Unlike other DNA-based, molecular screening options, Promega MSI technology uses five monomorphic mononucleotides, which is recommended by the National Cancer Institute,” says Jeff Bacher, PhD, senior research scientist at Promega. “Our test uses a sensitive and specific panel of markers for detection of MSI status, and offers valuable insight to help inform physicians on how best to treat patients with cancer—including those likely to benefit from immune checkpoint inhibitor treatment.”

For more information, visit the Microsatellite Instability Resource Center at Promega.