Transforming cancer therapy by targeting the extracellular matrix.
Today’s cancer therapies rely primarily on targeting cancer cells, as the obvious agent of disease. Yet as cancers metastasize, spreading throughout the body, therapies often begin to fail—and it is these metastatic cancers that are responsible for 90% of deaths. Cancer patients have an urgent need for new therapeutic approaches that look beyond primary tumors, and new diagnostic techniques that can detect metastases sooner.
Matrisome Bio, co-founded out of MIT by Noor Jailkhani, Richard Hynes and Sangeeta Bhatia, has developed a therapeutic platform with a novel target: the extracellular matrix, the dense network of proteins that surround the cells in our bodies. Using newly developed nanobodies as its instrument, Matrisome Bio sees a path to transform the landscape of care across chronic diseases, beyond cancer. ”The matrisome represents a huge and yet under-explored therapeutic opportunity,” says Jailkhani, CEO. “We are combining disease expertise, technical know-how, and an entirely new suite of proprietary tools, to deliver diagnostic and therapeutic payloads.”
The extracellular matrix’s complex meshwork of highly cross-linked proteins is a fundamental structure of multicellular animals, and a crucial factor in cancer biology. While tumors are generally understood as consisting of dividing cancer cells, in some tumors from 25% to 90% of their mass is actually extracellular matrix. That tissue ECM differs between its healthy and diseased states—both in composition and abundance. “The matrix is an underappreciated goldmine,” says Hynes, a Lasker Award-winning biologist, who over five decades has systematically been studying what has come to be known as the "matrisome," i.e. the ensemble of extracellular matrix and its associated proteins. This extensive work with patient samples revealed that certain specific matrix proteins appear across tumor types, in primary tumors as well as metastases. The insight presented an intriguing therapeutic approach: rather than following the dictates of precision medicine, and going after the unique mutations in an individual patient, the matrisome offers a target that is often consistent across disease sites, among patients, and between cancers. “The matrix is more stable than cancer cells. It has fewer mutations, and it is very, very, abundant,” says Jailkhani. “It’s a really exciting new target.”
Jailkhani’s research in the Hynes Lab developed single domain antibodies (nanobodies) that selectively bind proteins in the tumor matrix, along with the techniques needed to use them for the delivery of both therapeutic and diagnostic payloads. The resulting proprietary libraries of nanobodies now form the foundation of Matrisome Bio’s innovative approach. With the help of Bhatia—a longtime collaborator of the Hynes lab, experienced biotech entrepreneur, bioengineer, and clinician—Matrisome Bio is advancing its unique nanobody delivery vehicles from bench to bedside. Specific nanobodies are ready for validation against matrix targets, with each bringing the potential to deliver an entirely new suite of clinical tools.
While cancer therapeutics are the clear initial applications, Matrisome Bio is working to develop a nanobody platform useful in delivering therapeutics for a broad range of diseases. “Patients have so many needs that are not addressed today—like fibrosis, cardiovascular diseases, and others," says Jailkhani. “We aspire to use our knowledge of the matrisome, in healthy and disease conditions, to create a new class of therapeutic applications.” Along with its own internal pipeline, Matrisome Bio is also pursuing opportunities for partnering with the breadth of innovative payloads now transforming medicine.
“One of the great challenges in therapeutics today is finding novel targets, supported by deep scientific validation, coupled with modalities that are mature enough to have a clear path to patients,” says Bhatia. “Matrisome Bio represents such a transformative opportunity.”