Written by:
Senior Vice President, Cell Therapy Portfolio Development and Operations, AstraZeneca
Global Head of Multiple Myeloma, Clinical Development and Strategy, AstraZeneca
Global Clinical Strategy Head, Late Development Oncology, Cell Therapy, AstraZeneca
Cell therapy plays a pivotal role in our ambition to eliminate cancer as a cause of death. At AstraZeneca, we are advancing multiple strategies aimed at improving the effectiveness of cell therapies and expanding global access to this innovative therapy.
For many people living with cancer, treatment can mean ongoing cycles of therapies. Cell therapy offers hope as a potential one-time treatment, with the possibility of driving deep, durable responses and, in some cases, cure.
Since the first chimeric antigen receptor T-cell (CAR T) therapy was approved in 2017, cell therapy has transformed outcomes for certain blood cancers, including lymphomas and multiple myelomas, and is now showing early promise in solid tumours.1 Known as autologous cell therapies, currently approved CAR Ts involve isolating a patients’ own T-cells and genetically modifying them to deliver a highly personalised therapy that targets their tumour.
Advancing a diverse toolkit across haematological malignancies
At AstraZeneca, we are advancing a diverse toolkit across haematological malignancies, including next‑generation cell therapies. Autologous cell therapy has transformed outcomes in certain blood cancers, but its bespoke nature requires specialised manufacturing and a clinical journey that is time‑intensive and challenging to deliver at scale.2 To address these challenges, we are progressing multiple approaches: accelerating autologous cell therapy manufacturing, and advancing off-the-shelf approaches, such as allogeneic and in vivo cell therapy. These approaches aim to overcome barriers and bring cell therapy to more patients globally.
A key focus for our Haematology teams is developing more effective therapies for Multiple Myeloma (MM). Advances in immunotherapies and targeted treatments mean that many people live with MM as a chronic condition, but this comes with a heavy treatment burden. Frequent hospital visits, intensive monitoring and the possibility of relapse can take a significant physical and emotional toll on patients and their loved ones.3,4
Diagnosed with multiple myeloma at 43, I was overwhelmed. This illness touches every part of my life - not just my body, but my peace of mind, my ability to work and my daily freedom. Frequent clinic visits, relapse after conventional therapies, long waits for CAR T manufacturing, brought constant uncertainty for my family and me. All I longed for was a care that lets me live treatment-free and feel like myself again – not just a patient.
Guided by this need, we are exploring approaches that have the potential to make a tangible difference on the burden of treatment for people living with MM.
Next-generation manufacturing
Our rapid autologous manufacturing platform, pioneered by Gracell, is designed for optimal T-cell activity, aiming to deliver fitter CAR Ts. It also shortens manufacturing timelines, aiming to reduce treatment wait times and the risk of disease progression before infusion.
In parallel, we are committed to moving CAR T into earlier lines of disease, where lower tumour burden and less complex disease biology may increase the likelihood of deeper, more durable responses, and even the potential for curative outcomes. Together, these efforts seek to ease the day-to-day burden of care and extend the potential benefits of cell therapy to more patients.
How is cell therapy advancing the treatment of solid tumours?
Replicating the success seen in some haematology indications in solid tumours is core to our cell therapy ambition. However, there remain substantial challenges to overcome.1 The tumour microenvironment (TME) is complex and hostile, containing cells and molecules that weaken or inhibit immune responses, and this can suppress the activity of cell therapies. It also provides a physical barrier that limits their ability to effectively infiltrate, accumulate and persist in the tumour.1,5 In addition, current CAR T-cell therapies target extracellular antigens, leaving many tumour-associated targets inaccessible. Solid tumours are also often highly heterogeneous, particularly in advanced disease, meaning that targeting one antigen may not always be sufficient.6
To be successful in solid tumours, cell therapies will need to overcome these barriers. One important step is the development of ‘armouring’ technologies to enable engineered T‑cells to resist immunosuppressive signals within the tumour microenvironment. Informed by promising preclinical findings, our scientists have developed TGFβ-armouring strategies, designed to block TGFβ signalling and help cell therapies remain active in the tumour microenvironment for longer. Our most advanced armoured cell therapy has demonstrated early clinical signals in hepatocellular carcinoma consistent with target engagement and CAR T activity within the TME.7
Armouring cell therapies to resist the hostile TME
Alongside CAR Ts, which target extracellular proteins, we are advancing T-cell receptor therapies (TCR T), a type of cell therapy that is engineered to identify intracellular proteins presented on the cell surface by major histocompatibility complex (MHC) molecules. TCR Ts create new ways to precisely target intracellular antigens, including cancer specific mutations in genes such as KRAS and TP53. Beyond this, we are exploring multispecific cell therapies approaches targeting more than one antigen to better address tumour heterogeneity.
By advancing a broad pipeline of CAR Ts and TCR Ts, our aim is to deliver a range of potential new treatments that aim to improve outcomes across hard-to-treat cancers such as prostate, liver and pancreatic cancer. Looking ahead, we are exploring how cell therapies could be evaluated earlier in the disease course, when tumour burden is lower and the biology less complex, conditions that may potentially be more favourable for therapeutic impact.
CAR T-cell therapy in solid tumours
Designing the future of cell therapy deilvery
For innovation to translate into real-world impact, it must be broadly accessible. To help realise this, we need to simplify treatment pathways and bring cell therapy into the outpatient setting, reducing disruption to patients’ daily lives and easing pressure on healthcare systems. Close collaboration across industry, academia, healthcare systems and clinical sites from the outset is essential to delivering clinical trials and care models that reflect patient needs and operational realities.
Regulatory frameworks are also evolving. Continued engagement among regulators, clinicians and industry is helping to accelerate pathways for innovative therapies while ensuring rigorous oversight is maintained.
In parallel, we are exploring innovative technologies, including in vivo platforms, to enable delivery of off‑the‑shelf cell therapies. We’re focused on improving scalability to broaden access and reduce wait times associated with bespoke manufacturing.
Our visionary approach goes beyond what’s possible today. Looking to the future, we are pioneering cell therapy at scale, investing in state-of-the-art platforms, building global capabilities, and working to extend the impact of cell therapies. This includes going beyond blood cancers to solid tumours, and into disease areas beyond oncology. Our goal is to ensure more patients can benefit from cell therapy worldwide.
What science can do next
Our world‑class cell therapy R&D and manufacturing capabilities, strengthened through our strategic acquisitions and partnerships, are enabling us to build a diverse and flexible cell therapy toolkit.
Looking ahead, we are actively helping shape the future of cell therapy by integrating outpatient delivery models and exploring scalable, off-the-shelf platforms. These innovations aim to make cell therapies more accessible for patients and lessen the burden on patients and healthcare systems alike. With each step, we move closer towards our vision where in the future, physicians can select from libraries of patient‑ready cell therapies tailored to the specific biology of each patient’s disease. With this continued innovation and collaboration, cell therapies have the potential to transform the future of cancer care.
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.
References
- Mitra A, et al. From bench to bedside: the history and progress of CAR T cell therapy. Frontier in Immunology. 2023. 15;14:1188049.
- Lee NK, et al. Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation. Ann Lab Med. 2024. 44(4):314–323.
- Fu C, et al. Redefining multiple myeloma treatment: Advances, challenges, and future directions in immunotherapy. Chin Med J. 2025. 8;138(19):2399–2410.
- Hulin C, et al. Living with the burden of relapse in multiple myeloma from the patient and physician perspective. Leuk Res. 2017;59:75-84.
- Fonkoua LA, et al. CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities. Mol Ther Oncolytics. 2022;25:69–77.
- Zhu L, et al. A narrative review of tumor heterogeneity and challenges to tumor drug therapy. Ann Transl Med. 2021;9(16):1351.
- Zhang Q, et al. GPC3-specific dnTGFβRII-armoured CAR T cells for hepatocellular carcinoma. Nature. 2026. Online ahead of print. doi: 10.1038/s41586-026-10786-z.
