Written by:
Gordon Moody
Senior Director, Cell Therapy, Oncology R&D, AstraZeneca
A major focus for our Oncology Cell Therapy Unit is on replicating the success achieved with cell therapies in haematologic malignancies in solid tumours. A further ambition is increasing their accessibility to patients by delivering patient-ready, off-the-shelf therapies. To achieve these goals, we have invested heavily in building our expertise and capabilities - from genetic editing and engineering to in-house manufacturing and expanding clinical operations and development.
The immune system – the first line of defence
The immune system controls the initiation of diseases such as cancer, and T cells are fundamentally involved in preventing the emergence of cancer by surveying the body to identify and eliminate foreign or cancerous cells.1,2 However when cancerous cells escape detection by the immune system, tumours can develop. As cancer becomes treatment refractory and continues to progress, it can also evolve new ways to evade or suppress the activity of T cells.3
Advancing today’s cell therapies and developing tomorrow’s cancer breakthroughs
Cancer treatment has advanced beyond small molecules and biologics, and we are in an exciting era during which we can utilize engineered T cells — so called “living drugs” — as medicines.4 Since the first chimeric antigen receptor T cells (CAR-T) approval in 2017 the field has been growing exponentially, largely dominated by the development of therapies to treat haematological cancers.5 It’s one of few modalities that has driven cures.4 However, there is still more to do to position cell therapy as a mainstay of future cancer treatment regimens.
Current approaches in oncology are largely focused on autologous CAR-Ts, where T cells are extracted from a patient and genetically modified to recognise their specific cancer.4,6 Although these can be highly effective, each CAR-T product is made for a single patient, which is time consuming and leads to variability in quality of the cells manufactured. Additionally, the need for a complex and specialised infrastructure to enable extraction, engineering and supply of a patient’s T cells limits the accessibility of these medicines. Our vision is to develop a library of patient-ready ‘off-the-shelf’ therapies, utilising cells from healthy donors, rather than patients, to help overcome these challenges. Having the right manufacturing capabilities is crucial to deliver this vision. Our internal efforts in manufacturing will attempt to address and overcome these complexities.
Replicating the success seen in blood cancers with cell therapies in solid tumours has been challenging. It is well established that the hostile tumour micro-environment can hamper the infiltration, function, and expansion of transferred T cells.7 Our research group at AstraZeneca is focused on solving these challenges. Advances in our understanding of immune function in suppressive conditions are informing novel ways to genetically manipulate T cells to improve their activity and persistence to provide longer lasting anti-tumour immunity. Our researchers are developing a portfolio of armouring molecules that are designed to combat and reverse immunosuppression and exhaustion, for example by blocking the activity of TGF-beta.
Learn more about how our researchers engineer CAR-Ts to overcome barriers that limit their effectiveness in solid tumours in this video:
Beyond CAR-Ts - T cell receptor targeting
Building on our efforts in CAR-Ts, we want to expand cell therapy to new targets in cancer biology. We are researching the potential of T cell receptor (TCR) engineering, which has shown early promise in the clinic. While CAR-Ts target antigens on the surface of cancer cells, TCR therapies (TCR-Ts) can target intracellular proteins, potentially unlocking new opportunities in cell therapy.8
Expanding our capabilities in TCR therapy, we recently acquired Neogene Therapeutics Inc., a leading biotechnology company pioneering the discovery, development and manufacture of TCR-Ts. Their skills in TCR-Ts complement our in-house cell therapy capabilities, allowing us to accelerate our research in this field, a vital part of our plan to bring curative cell therapies to patients.
Ultimately, by uncovering new targets and devising strategies to improve the precision and effectiveness of cell therapies, our goal is to deliver new medicines that have the potential to transform cancer care and patients’ lives.
Join us: Developing the next wave of cell therapies to target cancer
We welcome committed, talented cell therapy scientists to join us on what promises to be one of the most exciting, stimulating and rewarding journeys in 21st century medicine.
Our end-to-end approach brings the pieces together: expertise in biologics engineering, gene-editing, immunology and commercialisation, and access to cutting edge technologies and in-house manufacturing capabilities that facilitate innovation.
A leader in Oncology with a global footprint, we are growing a differentiated pipeline to address a range of tumour types associated with significant unmet need. There are limitless opportunities to make your mark, take smart risks and pioneer new ideas. Diverse in experience and approach, our team shares a passion for the science and drive to discover what’s possible and an ambition to be leaders that take cell therapy in new directions.
We recruit scientists with relevant expertise to join us in our state-of-the-art research facilities in Cambridge, UK, and Gaithersburg, US.
