In the long-running quest to improve on chemotherapy, monoclonal antibodies offered a major advance by mobilizing the immune system to attack cancer cells. While monoclonal antibodies bind to a single target, bispecific antibodies are engineered to bind to two targets at once, bringing new possibilities for precision-guided cancer immunotherapy. They may also serve as delivery vehicles for other therapeutic molecules, including CRISPR components, small interfering RNAs and viral vectors used in gene therapy. Jessica Kirshner’s team at Regeneron is accelerating progress in the field, developing tailored immunotherapies that could bring new hope to patients with limited therapeutic options.
What are bispecific antibodies?
Natural antibodies are specialized, Y-shaped proteins from the immune system that can identify potential threats like bacteria and viruses. We engineer bispecific antibodies to express a pair of arms that each bind a different target. For example, one arm can bind to a protein called CD3 on the surface of immune cells called T cells, while the other arm binds to a selected target protein on cancer cells. The goal is to bridge T cells to cancer cells and use tumor antigens to cluster the CD3 signaling molecules on the T cell surface. This leads to T cell activation, so the T cells can attack the tumor cells and kill them.
What distinguishes bispecific antibodies from other cancer therapies?
Bispecific antibodies bring multiple tumor-cell-killing mechanisms into play simultaneously. When a T cell is activated and locked on to a cancer cell, it triggers other downstream mechanisms within the immune system to battle the tumor.
A lot of the work we do at Regeneron involves identifying and characterizing tumor-specific targets. We can also adjust the strength with which the antibodies bind to their target cells, which allows us to control the intensity of the immune response and help ensure safety.
How could bispecific antibodies deliver other therapeutic molecules?
Since we characterize the structures and amino acid sequences of our proteins, we can find the best locations for attaching therapeutic molecules without disrupting antibody function. Bispecific antibodies allow for highly specific and targeted delivery. We can transport drug molecules to tumor cells and diseased organs throughout the body, and design an antibody so it can infiltrate a cell and bring its therapeutic cargo along with it.
How does Regeneron ensure the safety and quality of its bispecific antibodies?
Our proprietary VelociSuite technology platform produces fully human antibodies. We produce the antibodies in a single cell line, which allows for very straightforward purification. Almost all of our antibody design and manufacturing is conducted in-house, so we have end-to-end control over the process, which is unusual in this industry, and which ensures the quality of the therapy.
What are your goals with bispecific antibodies?
Our goal is to transform cancer care. In the short term, we’d like to get better at treating solid tumors, which are still a big challenge for immunotherapy. Blood cancers provide more accessible targets for therapy; solid tumors are more dense and complex, and their cells are more difficult for T cells to attack. But with our abilities in antibody engineering and capacity to deliver other therapeutic molecules, I’m optimistic we can continue to make real progress.
Find out more about Regeneron’s commitment to transforming cancer care.
