On October 26, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, and the NSABP Foundation, Inc. (NSABP), an academic research organization supported by the National Cancer Institute (NCI) and industry funding, reported that they have entered into a research agreement to jointly characterize the immunophenotypes of colorectal cancer samples using the PanCancer IO 360 Gene Expression Panel, a highly-multiplexed gene expression panel designed to identify targetable pathways of tumor and immune biology (Press release, NanoString Technologies, OCT 26, 2017, View Source [SID1234521189]).
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Under this collaborative agreement, NanoString and the NSABP will use the NanoString nCounter Analysis System to study colorectal cancer tumor samples from the NSABP biobank. The NSABP’s MPR-1 Patient Registry and Biospecimen Profiling Repository is a bank of over 2,500 tumor tissue specimens collected from patients with metastatic colorectal cancer. The comprehensive characterization of the tumor-immune microenvironment in the NSABP samples has the potential to identify novel biomarkers for different mechanisms of immune evasion in colorectal tumors.
The PanCancer IO 360 Panel assays key pathways from the tumor, the microenvironment and the immune system and includes more than 20 signatures that are potentially associated with therapeutic response to novel therapeutic agents with “matched” mechanisms of action. These signatures include defective DNA mismatch repair (dMMR) – the genetic abnormality causing high microsatellite instability (MSI-H), which is particularly relevant in this tumor type and is associated with high response to PD-1/PD-L1 blockade. Interrogation of colorectal tumor samples from the NSABP repository with the PanCancer IO 360 Panel will test the concordance between dMMR status as assessed by the NanoString PanCancer IO 360 Panel and the standard immunohistochemistry (IHC) approach.
The collaborators will use the PanCancer IO 360 Panel to explore biological pathways of immune resistance including NanoString’s Tumor Inflammation Signature (TIS), recently described by Ayers, et al. (View Source), which measures the presence or absence of a peripherally suppressed adaptive immune response within the tumor. For example, TIS was found to be predictive of response to pembrolizumab, and pembrolizumab’s mechanism of action is believed to unleash a pre-existent adaptive immune response by inactivating the inhibitory activity of this receptor. NanoString and NSABP hypothesize that the Tumor Inflammation Signature (TIS) could identify a larger population of tumors potentially responsive to PD-1 blockade than MSI/dMMR status alone, because the TIS directly measures downstream tumor inflammation that can result from multiple different mechanisms (in addition to high mutation load).
“Anti-PD-1 and anti-PD-L1 antibodies have demonstrated significantly durable efficacy in patients with metastatic MSI-H colorectal cancer. Unfortunately, this subset of patients represents only about 5% of stage IV CRC patients, leaving the vast majority of this population in great need of effective treatments,” said Alessandra Cesano, chief medical officer at NanoString. “The combination of NanoString’s powerful technology and the NSABP’s expertise and extensive research biobank of colorectal tumor samples holds great promise for the discovery of new targets that will help us to fight this devastating disease.”
“It is critical to find better ways of identifying colorectal cancer patients who will benefit from current immunotherapeutic approaches as well as improving our understanding of the mechanisms of resistance at the molecular level,” said Dr. Samuel Jacobs, Director of Medical Affairs for the NSABP. “It is our hope that this collaboration with NanoString will deepen our understanding of the mechanisms of tumor immune evasion in order to guide the successful development of novel immunotherapeutic approaches and combinations.”