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Introducing ‘Immuno-Materials’ to immunotherapy

In the Wyss Institute’s ‘Immuno-Materials’ Focus Area, institute researchers develop material-based systems capable of manipulating immune cells in the human body to treat or diagnose disease

Dysfunction of the immune system underlies many diseases, including cancer and autoimmune disease. Further, it is increasingly recognized that immune cells actively regulate tissue regeneration. Advances in our understanding of the human innate and adaptive immune systems thus promise to revolutionize the treatments of many diseases. However, strategies to effectively program an immune response, and reprogram undesired responses, by manipulating a patient’s immune cells are in their infancy.

The Immuno-Materials (IM) Focus Area will invent and develop biomaterials capable of concentrating, interrogating, and manipulating immune cells ex vivo and in the human body, in order to provide new treatments to patients. The fundamental concept underlying this strategy is that biomaterials can control in space and time the interaction of immune cells with immunomodulatory agents, leading to effective and safe approaches for immune cell programming and reprogramming. The resulting material systems are anticipated to have broad utility, including diagnosing and treating exposure to infectious diseases, generating cytotoxic T lymphocyte responses to cancer (therapeutic vaccines), and promoting pro-regenerative immune responses following trauma. This work will leverage inventions from leading academic laboratories at Harvard/Wyss and the affiliated Universities and Hospitals with the expertise within the IM Focus Area in the biomaterials, immunology and drug delivery fields, particularly as they relate to clinical translation of new devices.

Wyss Core Faculty, Dave Mooney, explains our Immuno-Materials Focus Area, which adds a new dimension to immunotherapy in that it harnesses materials to make treatments more efficient and effective. These material-based systems are capable of modulating immune cells and releasing them into the body where they can treat diseases.

As a dedicated Focus Area, ‘Immuno-Materials’ naturally evolved from the Institute’s vision of designing programmable nanomaterials, ‘smart’ nanotechnologies for regenerative medicine, immune engineering and targeted drug delivery inspired by natural biomaterials. Within the former ‘Programmable Nanomaterials’ (PMN) platform, a series of conceptually diverse technologies were invented.

Programming nanomaterials with new functionalities

At the basis of those technologies are molecular structures and systems that operate on the nano- and micro-scale leveraging the chemical and biophysical properties of nucleic acids such as DNA and innovative polymeric materials.

Scanning electron micrograph image of an injectable pore-forming scaffold material that self-assembles from so-called mesoporous silica rods (MSRs) after being injected under the skin. Credit: Wyss Institute at Harvard University

On one end of this spectrum, Wyss Institute researchers have engineered nucleic acid-based nanostructures that self-assemble into predesigned shapes and complexes and functionalized them to perform different biomedical, analytical and structural tasks. Illustrative examples for these approaches are ‘DNA origami’ that self-assemble into higher-order structures; these highly defined architectural elements made of DNA can encapsulate and deliver drugs or package other molecular cargo. In another project, nucleic acid-based ‘nanoswitches’ have been engineered that can be made responsive to a range of different stimuli either to serve as diagnostic indicators or to actuate complex processes in synthetic systems and in living cells.

Other DNA-based technologies developed as programmable nanomaterials allow researchers to dicipher biological processes down to the level of single molecules. Such does the ‘DNA-PAINT’ suite of technologies enable super-resolution imaging of biomedical samples, even the counting of individual molecules within them, all on commonly available fluorescent microscopes. And in a different project, a technology called ‘Molecular Force Spectroscopy’ was developed that gives researchers the opportunity to observe multiple single molecules or single molecule interactions when exposed to mechanical forces that they would experience in the body in a regular bench top centrifuge. Through these technologies, highly sophisticated analysis is becoming possible on standard laboratory equipment.

On the other side of the materials spectrum, Wyss Institute researchers have designed and synthesized new biomaterials in form of polymeric hydrogels with various compositions and capabilities that can be delicately fine-tuned towards different purposes, tissue environments and physical responses. These hydrogels can be implanted into the body either to deliver drugs in a highly controllable manner, to provide desirable chemical cues with the ability to reprogram the behavior of interacting cells, and they have been used to release cohorts of stem cells with regenerative potential for the repair of different degenerating or injured tissues. Polymeric hydrogels have also been used by the researchers to create highly adapted membranes like the so-called 3-D printed tympanic membrane that can be implanted into the ear to improve hearing. Recently, even methods to embed single cells in microgels to achieve enhanced regenerative abilities have emerged as products of the Wyss Institute’s focus PNMs. In their entirety, these and other very specifically engineered biomaterials have become linchpins of a series of pioneering drug testing and delivery, tissue engineering, and immunotherapy approaches.

Evolving immune- from programmable nanomaterials

In particular, the arising opportunity to re-educate the immune system with the aim to direct its cell killing properties toward tumor tissue has led to the notion of a new type of vaccine that in the future could be applied to fight a larger array of cancers and infectious diseases, and to confront other health and problems. This outlook prompted the Wyss Institute to launch ‘Immuno-Materials’ as a new Focus Area that utilizes much of the materials expertise amassed in the PMN platform.

This image shows a scanning electron micrograph from a biomaterial (red), that, when introduced into the body, attracts immune cells like so-called dentritic cells (yellow) and re-programs them to perform therapeutic functions. Used in cancer immune-therapy, dendritic cells will enter nearby lymph nodes to orchestrate an effective immune-response that can eradicate a tumor. Credit: Wyss Institute at Harvard University

In pioneering Immunomaterials work, researchers from the Wyss Institute and the Harvard School of Engineering and Applied Sciences (SEAS) have provided proof-of-concept that a porous biomaterial can be engineered to take up and immobilize tumor cell components derived from human melanoma samples like a sponge, and, in addition, bind immune-stimulating molecules. When injected into animals bearing the same type of tumor, they stimulate a special type of immune cell, called a dendritic cell, to orchestrate an effective immune response that is able to effectively shrink the actual tumor mass. Together with clinical collaboration partners at the Dana-Farber Cancer Institute in Boston, Massachusetts, this groundbreaking potential is now being tested in clinical trials with human melanoma patients.

Insights into how the immune system can be redirected towards disease-causing cells and organisms have spawned a number of promising new trends within the burgeoning field of immunotherapy. Work in the Wyss Institute’s Immuno-Materials Focus Area is bringing a unique materials approach to immunotherapy that harnesses existing knowledge and therapies, and creates new ones for areas in need.

Inspired by the Wyss Institute’s first cancer vaccine, analogous, yet highly tailored materials-based vaccine approaches are currently being developed to fight other major health hazards. An expanding team of researchers and clinicians, including new Associate Faculty members with world-leading expertise in immunobiology and immunotherapy, will aim to tackle other amenable types of cancer, infectious and autoimmune diseases, certain addictions, and test their concept as an animal contraceptive vaccines in veterinary medicine.

At the same time, Institute researchers are also exploring alternate materials including nucleic acids as innovative vehicles for cells and therapeutic molecules that would allow the remodeling of immune responses. With this shift in focus from ‘programmable nanomaterials’ to ‘immuno-materials’ and the integration of immune-related efforts from other focus areas, the Institute is venturing into new and exciting territory bringing its unique experience to bear on several therapeutic areas.

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