Fighting cancer using a novel cell engineering technology

Effective intracellular delivery has been a long-standing ambition for scientists. Often cancerous cells have faulty intracellular proteins, and delivery of novel therapeutics to address these targets is an ongoing challenge, despite decades of research. Massachusetts Institute of Technology (MIT) researchers Robert Langer and Klavs Jensen, both distinguished professors of chemical engineering, and award-winning scientist Armon Sharei, felt driven to address this challenge.

By the time the team started their investigations, novel cell therapy approaches, such as early CAR-T therapies that target surface receptors associated with a specific cancer, had started to come to fruition. However, healthy cells can also express these surface receptors, which limit potential applications of CAR-T therapies.

The multi-disciplinary MIT team was determined to find a way to target intracellular proteins by delivering molecules and other materials directly inside cells to change their function. The ability to engineer cells in this way could potentially be applied to any cell type, and lead to a more effective cell-based therapy platform.

Armon Sharei completed his doctoral research with the discovery that by squeezing cells and thereby opening gaps in the cell membranes, materials can be delivered inside cells.

During his PhD studies in Klavs Jensen’s and Robert Langer’s laboratories at MIT, Armon Sharei found that suspending cells in a buffer and then pushing it through a microfluidic chip, squeezes the cells and stretches their membranes opening gaps, which in turn enable the delivery of a diversity of materials into the intracellular space. Afterwards, the cells repair their membranes, and materials such as therapeutics interact with the targets inside the cells to trigger the desired response.

Further research and validation confirmed that this technique enabled a rate of up to 100-times higher delivery than other existing methods – chemical, electrical or biological – for challenging applications, and with minimal toxicity.

In 2013, the team founded SQZ Biotech, as an MIT spin-out, and named their technology platform Cell Squeeze.

Aware of Roche’s wealth of clinical experience in oncology, Robert Langer facilitated an initial connection between SQZ Biotech and the Roche Partnering team. The two organisations quickly saw the great potential of this technology and the productive dynamics between the scientific teams.

The Roche Partnering teams also have a long-standing relationship with leading academia centres, including MIT, and a proven track record in adopting new potential technologies with commercial application and employing them for successful development of novel therapeutics.

Consequently, Roche and SQZ Biotech formed a partnership expecting to leverage SQZ’s pioneering technology to engineer B cells as a therapeutic platform for a broad range of cancers. The goal is to deliver antigens into B cells, which will help activate killer T-cells to fight tumours.

The collaboration involves scientific teams in both organisations working together to assess the validity of this approach, whereby a patient’s own immune system is manipulated to be able to fight tumours more effectively than current cell therapies. The ability to engineer such a response is fundamentally dependent on effective delivery of tumour-associated proteins, or antigens, into a patient’s B cells.

This delivery process is uniquely enabled by the cell squeeze technology, which makes it possible to simultaneously insert a specific compound into the cell during the squeeze and activate a patient’s own immune system.

• 2011: Armon Sharei discovers CellSqueeze technology

• 2013: SQZ Biotech is founded as a spin-off of the Massachusetts Institute of Technology

• 2015: Roche and SQZ Biotech announce their partnership