Engineering Cancer Therapeutics

22 July 2024

Flouresence microscopy image of a cancer cell surrounded by killer T cells, illustrating how CAR-T therapies work. Image courtesy of the NIH Image library.

Can we apply engineering biology principles to develop kinder, more effective treatments for cancer? From innovative CAR-T therapies, to new tools for drug discovery and potential new treatments. Learn more about the University of Cambridge researchers exploring precision medicines for cancer.

Engineering biology has transformative potential in healthcare. It could make drug production greener with engineered plants, lead to new diagnostic tests, and design personalised treatments. Exciting cancer breakthroughs include cell-based immunotherapies, like CAR-T therapy. And more recent advancements include nucleic acid therapies and synthetic cells for drug-delivery.
At the University of Cambridge, researchers are exploring a wide variety of possibilities. Dr Mike Chapman's lab is tackling multiple myeloma with innovative CAR-T therapy. Prof Mark Howarth's lab is advancing protein engineering with the SpyTag/SpyCatcher system. Prof Laura Itzhaki's lab is investigating cancer-causing proteins and designing potential new treatments. These are just a few examples of the Cambridge academics working in this exciting new area.

Improving CAR-T Immunotherapies

Dr Mike Chapman, Dr Georgina Anderson and Dr Ieuan Walker

Mike Chapman's lab works on understanding and treating multiple myeloma (MM). This is a particularly aggressive form of blood cancer. One promising treatment for MM is CAR-T therapy. It involves editing a patient's immune cells to target cancer cells. The cells are then put back into the patient's bloodstream to find and attack cancer cells. One problem with using CAR-T therapy is that sometimes the edited cells also recognise and attack healthy tissue. This can cause unwanted side effects. Postdoctoral Fellow Dr Georgina Anderson and PhD student Dr Ieuan Walker are working on ways to solve this problem.

Their work uses 'AND' and 'NOT' logic gates and takes complementary approaches. With AND gates, the cells have to recognise two parts of the cancer cell, making it less likely that they will attack healthy cells. With NOT gates, the cells recognise healthy tissue and know not to attack it. Both methods aim to reduce side effects and improve treatment efficiency. Both researchers are currently testing their systems on new combinations of targets. They are also sharing their methods to help others develop more specific treatments.

CAR-T cells using AND of NOT logic gates could help reduce treatment side effects.

CAR-T cells using AND of NOT logic gates could help reduce treatment side effects.

New Antibody Combinations for Drug Discovery

Prof Mark Howarth

Mark Howarth's lab works on engineering proteins for new therapies and vaccines. The lab has developed the SpyTag/SpyCatcher system. This is a tool that sticks proteins together, allowing them to work in new ways. One application of this technology is to create ‘bispecific antibodies’. These are antibodies that recoginse more than one part of a cell. Engineered antibodies are very useful for treating cancer, as they can recognise specific parts of cancer cells. Bispecific antibodies can be even more useful, as they recognise multiple parts of a cell and can have multiple antitumor effects.

Recent work in the Howarth lab has developed a system called SpyMask. This process allows them to quickly assemble, screen and purify different antibody combinations and conformations. The group have now tested their system on a common cancer target (HER2). In the future, they believe that this new tool could help to accelerate and fine-tune cancer drug discovery.

The SpyMask method can produce and screen new antibody combinations for better treatments.

The SpyMask method can produce and screen new antibody combinations for better treatments.

Nanobodies to Correct Cancer Mutations

Prof Laura Itzhaki

Laura Itzhaki's lab works on a class of proteins known-as tandem-repeat proteins. These proteins are made up of repeated structural motifs that form elongated spring-like structures. They are important as they are often altered in human diseases.Because of their repetitive structures, these proteins are easy to modify and redesign. Laura’s group is using redesigned tandem-repeat proteins in several ways. This includes engineering them to help get rid of disease-causing proteins. They are also designing small molecules, peptides and proteins to target tandem-repeat proteins that cause diseases.

For example, they have developed antibody-like molecules called nanobodies that can correct the malfunction of a tandem-repeat protein called p16. Mutations in p16 can cause changes to its shape and structure. These changes can sometimes cause cancer. The Itzhaki lab has shown that nanobodies can correct these changes and stabilise the structure of p16. They hope that these antibodies could be used to help treat cancer. Laura's lab has also recently been awarded to new grants (BBSRC Engineering Biology Mission Award and a Cambridge Isaac Newton Trust Strategic Grant) which will help to establish protein library screening facilities. These new facilities will allow faster development and screening of potential new treatments, and bolster engineering biology research in Cambridge.

A nanobody against the tandem repeat protein p16 could help to stabilise its structure and correct for cancer-causing mutations.

A nanobody against the tandem repeat protein p16 could help to stabilise its structure and correct for cancer-causing mutations.

These examples show how engineering biology is paving the way for new and improved cancer therapies. Researchers at the University of Cambridge are at the forefront of these exciting developments, and are continuing to find new ways to develop kinder, more effective treatments.

Learn More

Learn more about how researchers at the University of Cambridge are changing the story of cancer and explore the engineering biology researchers involved in biomedical research.

Further Reading

How is engineering biology transforming healthcare?

How is engineering biology transforming cancer treatment?

AND and NOT gated CAR-T Cell Therapies

p16 and Making use of Tandem-Repeat Proteins

SpyTag, SpyMask and Bispecific Antibodies

Author Information

Dr. Stephanie Norwood
Coordinator and Events Manager
Engineering Biology IRC
University of Cambridge

Credits & Acknowledgements

Many thanks to Dr Mike Chapman, Dr Georgina Anderson, Ieuan Walker, Dr Mark Howarth and Laura Itzhaki for sharing their work with us.

Headline image: Flouresence microscopy image of a cancer cell surrounded by killer T cells, illustrating how CAR-T therapies work. Image courtesy of the NIH Image library: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths.