Cutting across discipline boundaries: Bioengineering meets T-cell therapy

Of all the forms of cancer common in the United States, lymphoma is a particularly tragic type of the disease. Considering the approximately 100,000 new cases diagnosed every year, developing more successful methods to treat lymphoma is very important. Traditionally, this condition is addressed with a combination of chemotherapy and radiation—both of which have effects that can be seriously damaging themselves. Dr. Matthias Stephan will lead the development of an alternative approach—one that programs the patient’s existing immune system to specifically attack the cancer, and thereby circumvents the damaging consequences of systemic chemical treatments. His research has established that microscopic gene-carrying nanoparticles engineered to target T lymphocytes can instruct them to destroy cancer-causing cells—a method that is not only very successful, but also avoids harmful effects caused by existing alternatives. Next, he and his team plan to scale up the production of these programming nanoparticles to clinically relevant amounts, to document their FDA credibility, and to establish the safety of their medical applications in a large animal model. Stephan expects that the end result of this project will be a product ready for clinical testing. 

Affiliated Investigators

Matthias Stephan, M.D., Ph.D.

Fred Hutchinson Cancer Research Center and the University of Washington

Immunobioengineering is an emerging but rapidly growing industry. Originally centered on the creation of synthetic pathogen-mimicking vaccine particles, the field soon introduced a host of innovative materials and new concepts that served as the basis of many novel therapies. The Stephan lab is using next-generation nanomaterials to develop new cell-based immune-therapies and vaccines that can boost the body's natural ability to fight cancer and other diseases. 

Dr. Stephan began specializing in this area as a graduate student at Memorial Sloan-Kettering Cancer Center, where he pioneered auto-costimulation and trans-costimulation as molecular strategies to augment the function of lymphocytes in the microenvironment created by tumors During his postdoctoral training at the Massachusetts Institute of Technology, Dr. Stephan developed a nanoparticle-based strategy to provide autocrine sources of adjuvant growth factor that support adoptively transferred, tumor antigen-specific T lymphocytes. Much of this work became the intellectual and technical foundation for a Cambridge-based startup company (Torque Therapeutics, Inc.). The long-term goal of his ongoing research at Fred Hutch is to make immunotherapy more practical and widespread by creating unconventional treatments at the interface between materials science and immunology. For example, his group developed an innovation that allows cancer-fighting immune cells to be contained in a biopolymer and surgically implanted at tumor excision sites — which means they can begin eliminating residual cancer cells immediately. These interdisciplinary studies demonstrate for the first time that launching cancer-fighting immune cells from polymeric devices can prevent relapse, and furthermore provide a treatment option for inoperable tumors. More recently, his research group reported a strategy to program circulating T cells with tumor-recognizing activities, which avoids the complex laboratory protocols usually used to achieve this transformation.