August Issue of Lancet Medical Journal Features Breakthrough Study Decoding Immunological Challenges of Xenotransplantation

NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, announced today that a team of globally renowned researchers utilized two NanoString platforms, the nCounter® Analysis System and GeoMx® Digital Spatial Profiler, to decode the immune response following the transplantation of genetically modified pig kidneys into humans. The groundbreaking study featured in the August issue and an accompanying commentary of The Lancet medical journal produced fundamental new data on the first pig-to-human organ transplants. Insight from the 2021 study contributes to the ongoing success and duration of follow-on pig-to-human transplants heralded last week in The New York Times and Wall Street Journal.

The seminal research led by Alexander Loupy, MD, Ph.D., in cooperation with a global medical team, unravels the complex molecular characteristics of antibody-mediated rejection following the first and second-ever pig-to-human kidney transplants that occurred in 2021 at NYU Langone Transplant Institute. In an accompanying Lancet commentary, scientists praised the team “for laying the foundation for deeper assessment of xenoimmunology and establishing immunological research pathways to advance xenotransplantation.” They also commented on the importance of “state-of-the-art spatial techniques” to decipher transcriptional immune activation.

“We gained vital data and, for the first time ever, we were able to see what is happening immunologically in defined regions of the tissue,” said Dr. Loupy. “This data, enabled by NanoString’s platforms and an Allo - Xeno gene expression repository, allowed us to understand both the similarities and the novel aspects underpinning organ rejection in xenograft transplantation compared to human organ transplantation. NanoString’s nCounter and GeoMx instruments harmonized to create a holistic view of the immune response.” Researchers from the Paris Institute for Transplantation and Organ Regeneration, University of Paris, France’s National Institute of Health and Medical Research contributed to the study.

Xenotransplantation, the process of transplanting organs from animals to humans, is a crucial area of research dedicated to addressing the profound shortage of healthy human organs available for transplant patients. The groundbreaking experimental transplant surgeries performed by Dr. Robert Montgomery at NYU since 2021 involve patients in a state of brain death. Their families and ethical committees have consented to artificially maintain blood circulation during the transplants to advance scientific knowledge on xenotransplantation with the hope of offering more healthy organs for future patients.

The research team, including co-first authors of The Lancet study, Dr. Valentin Goutaudier and Dr. Alessia Giarraputto characterized the human immune response to the porcine kidney using bulk tissue transcriptome profiling on the nCounter Analysis System. Scientists used the nCounter Human Organ Transplant Panel, a process NanoString developed with the Banff International Classification Consortium. It is used by nearly one hundred global research institutions. The panel was adapted to xenotransplants by using bioinformatics-based pig and human gene sequences with homologies alignment. This analysis revealed a molecular architecture of antibody-mediated rejection, including interferon-gamma response, endothelial activation, macrophage activation, and injury repair response in the xenografts.

The GeoMx Digital Spatial Profiler was used next to isolate the immune response to specific regions of the kidney. The GeoMx Whole Transcriptome Assay revealed that antibody-mediated injury was mainly located in the glomeruli of xenografts, with significant enrichment of transcripts associated with monocytes, macrophages, neutrophils, and NK cells.

Drs. Loupy and Montgomery say their findings represent a treasure trove of new information for optimizing genetically modified pig models that may be useful in developing more advanced immunosuppressive treatments for future recipients of xenografts.

“An estimated 100,000 people are waiting for organ transplants in the United States. Thousands die on the wait list. Numbers like these drive us at NanoString to provide researchers with the tools they need to find innovative solutions to solve extraordinary medical challenges,” commented Brad Gray, President and CEO of NanoString. “We congratulate Dr. Loupy and his extended team on their findings and celebrate the on-going successful studies in humans.”

About NanoString Technologies, Inc.

NanoString Technologies, is a leader in spatial biology, offers an ecosystem of innovative discovery and translational research solutions, empowering our customers to map the universe of biology. The GeoMx® Digital Spatial Profiler is a flexible and consistent solution combining the power of whole tissue imaging with gene expression and protein data for spatial whole transcriptomics and proteomics. The CosMx™ Spatial Molecular Imager is a single-cell imaging platform powered by spatial multiomics enabling researchers to map single cells in their native environments to extract deep biological insights and novel discoveries from one experiment. The AtoMx™ Spatial Informatics Platform is a cloud-based informatics solution with advanced analytics and global collaboration capabilities, enabling powerful spatial biology insights anytime, anywhere. At the foundation of our research tools is our nCounter® Analysis System, which offers a secure way to easily profile the expression of hundreds of genes, proteins, miRNAs, or copy number variations, simultaneously with high sensitivity and precision. For more information, visit www.nanostring.com.

The NanoString logo, NanoString, NanoString Technologies, GeoMx, CosMx and nCounter are trademarks or registered trademarks of NanoString Technologies, Inc., in the United States and/or other countries.

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