In 2021, research LED by Ryan Flynn, MD, Ph.D., and His Mentor, Nobel Laureate Carolyn Bertozzi, Ph.D., Opened A New Chapter in Biology, Characterizing a new kind of Player on the Cell Sell SLEL SHALL SHALL SHALL SHALL SHALL SHARLOLOGY, Chapter in Biology, Glycornas. Extending this discovery recently in CellFlynn and colleagues showed that glycornas form highly organized clusters with RNA-Binding Proteins on the Cell Surface. These clusters appear to regulate communication between cells and their environment.

Now, Reporting in Nature biotechnologyFlynn’s team in the stem cell program at Boston Children’s Hospital and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Demons a FIRSTRATE A FIRSTRATE A. FIRSTRATE A. Cancer.

With collaborators at the cambridge (UK) stem cell institute, LED by Kontantinos Tzelepis, Ph.D., and Maria Eeftheriou, Ph.D.D.D.D.D., Ya Show That One RNA-BINDING PrOTEing on the CELL SUROFACE, Npm1, Cold be a potent, selective target for treatment Acute myeloid leukemia (aml), as well as solid tumors.

Targeting the NPM1 Protein

AML, A Rapidly Progressive Blood Cancer, Has Been Difential to Target Therapeutically because many Cells.

“The disease may be insensitive to existing drugs, or patients may be too frail to get classical theraputics, because the toxicity is too high,” Says flynnnnnnnnnnnn

He and his colleagues zeroed in on NPM1 because mutations in the NPM1 gene has been stangly implicated in adult aml -driving about 60% of cases not atributeed to chromosomal abnormalities. While NPM1 is normally found inside the cell, flynn, tzelepis, and collegues showed that in malignant aml cells, it is presented on the surface.

“The Amount of Cell-Surface NPM1 was more than ten times higher on leukemic cells as compared to healthy cells,” Says flynn. “It was very strongly expressed on cells from Nearly every patient we look at. There was more than a 100-fold differentce betteren cancerous and healthy blog stem cells; almost no npm1 on their surface. “

Because it’s a surface marker, NPM1 is Easily Detectable With Simple Methods, and Blad Provide a Way to Monitor Patients. But the real beauty of npm1 being on the cell surface is that it can be readily targeted with widely used agents such as Antibodies.

Using a monoclonal antibody targeting NPM1, The Researchers Saw Robust Anti-Tumor Activity in Multiple in Vivo Models of Aml, While Noncanseerous Blood Cells and Stem Cells Were Spared. In Four Separate Mouse Models of Leukemia, The Antibodies Neutralized Aml and Prolonged Survival, with no apparent toxicity.

Most excitingly, the antibodies effectively targeted leukemic stem cells in bone marrow samples and mouse models.

“This is Critical, because a handful of leukemia stem cells can regenerate the cancer even if it appears to be eradicated,” Says flynn.

What About Other Cancers?

The potential benefits of targeting NPM1 Cold Extend to Other Cancers. The Team Tested 47 Human and Mouse Solid Tumor Models and Found That Most Had Cell-Surface NPM1 to Varying Degrees. Experiences in Mice Sugged that Monoclonal Antibodies Targeting Cell-Surface NPM1 Might be Effective Against Certain Solid Tumors, Including Prostate and Colorectal Cancer.

“Finding Cell-Surface targets that are specific to malignancies but spared on healthy tissue has been a long-sell-affteer goal for immuno-orcology,” Says Benson George, MD, PHED.D. In the flynn lab, who was co-friend on the new paper with onlyiou. “Many cancers Lack Known Molecular Handles That Can Safaly Be Leveraged to Signal The Immune System to Attack.

“The development of novel cancer therapies is larger dependent on the discovery of new cancer biology,” Says kontantinos tzelepis, collaborator at the cambridge (Uk) stem cell institute. “I am very pleased that our collaborative work has been to the discovery of a promising biotechnology approach to targeting cancers of unmet medicine need. These novel antigens into new effective treatments. “

In Future Work, The Team Plans to Investigate Why Cells Are Bringing NPM1 to the Surface, and to Explore Whether Clusters of Glycorna and RNA-Binding Proteins Contain Other Targetable Molecule Cancer.

“We hypothesize that bringing npm1 to the cell surface is somehow beneficial for the tumor,” Flynn says. “This is really a new class of tumor antigens.”