Harnessing the Power of Cell Therapy

Cell therapy is a promising, rapidly advancing field with the potential to transform treatment across disease areas with significant unmet needs.

What is cell therapy?

Cell therapy refers to transferring new cells, or cells modified in a laboratory to achieve particular characteristics, into the body to prevent or treat a disease.

Such therapeutic cells are designed to:

• Remove diseased or dysfunctional cells

• Restore or modulate the function of the patient’s cells through the expression of factors or direct cell-cell interaction

  
  

Cell therapies can be classified based on their origin:

• Autologous cell therapy means cells are isolated and removed from the patient, modified outside of the body, and reinfused as a medicine

• Allogeneic cell therapy means cells are derived from a separate donor, whose cells can be unmodified or modified (for example, to recognize a patient’s cancer specifically)

  
  

Autologous cell therapies are produced by isolating a patient's T cells and engineering them in the laboratory so they can recognize and eradicate diseased or abnormal cells.

Our ambition in cell therapy

Our ambition is to realize the transformative potential of cell therapies for people living with debilitating diseases worldwide, including cancer, autoimmune conditions, and rare diseases. To achieve this, we are building world-class cell therapy capabilities, advancing our understanding of disease biology, and driving innovation in gene editing, biologics, and cell engineering.

Today, cell therapies are already driving meaningful benefits for some patients with blood cancer5 and are showing early potential for future use in solid tumors and autoimmune diseases.

However, significant barriers prevent more widespread adoption in terms of access, manufacturing, and scale. We are working to find innovative solutions to address these issues, bring cell therapy to more patients, and expand its use.

Advancing next-generation cell therapies for cancer treatment

Adoptive cell therapy (ACT), known as cellular immunotherapy, uses immune cells to target cancer.

Cell therapy is pivotal to our ambition to eliminate cancer as a cause of death, and we are exploring the promise of T-cell therapies in cancer treatment.

T cell therapies are created by isolating T cells (a type of immune cell) from the patient or healthy donor's blood and genetically modifying them to recognize and kill cancer cells. These modified cells are then grown in the laboratory and given to the patient by infusion.

Chimeric antigen receptor T cell therapies (CAR-Ts) are genetically modified to express a chimeric antigen receptor (CAR) that recognizes a specific, cancer-associated protein on the surface of tumor cells.

T cell receptor therapies (TCR-Ts) are created by engineering a patient’s T cells to express a T cell receptor (TCR) that recognizes intracellular targets, including tumor-specific mutations expressed by cancer cells. The TCR is found on the surface of T cells and recognizes targets bound to the major histocompatibility complex (MHC) on antigen-presenting cells.

We are advancing a diverse pipeline of innovative CAR-Ts and TCR-Ts at the preclinical and clinical stages for hard-to-treat solid tumors and hematological malignancies.

Transforming care of hematological cancers with cell therapies

Autologous CAR-Ts have been hugely successful in treating some types of blood cancer. We aim to build on this work, and we have expanded our hematology pipeline by acquiring Gracell Biotechnologies. Together, we are advancing novel CAR-Ts designed using their rapid manufacturing process, with the potential to treat hematological malignancies.

Expanding cell therapies to solid tumors

Extending cell therapy's success to solid tumors has proved challenging for the scientific community. Unlike blood cancers, where cancerous cells are more freely accessible to targeting with cell therapies, solid tumors' tumor microenvironment (TME) provides a physical and immunological barrier that limits their effectiveness.

We have developed innovative strategies to ‘armor’ our cell therapies so they can resist the immunosuppressive effects of TGFβ. This cytokine is highly expressed in many solid tumors and limits immune cell activity. We are using genetic engineering for our TCR-Ts and CAR-Ts to reduce immunosuppressive signaling, thereby enhancing the potential activity of cell therapy in solid tumors.

Our growing pipeline of CAR-Ts utilizes our novel armoring platform and targets hard-to-treat solid tumors. This includes therapies targeting gastric and pancreatic cancer, prostate cancer, and hepatocellular carcinoma. To complement our global development programs, we are collaborating with Chinese biotech AbelZeta Pharma to co-develop our CAR-T solid tumor portfolio in China and accelerate the development of potential new medicines for patients.

We aspire to be at the forefront of innovations in cell therapy, and our acquisition of TCR-T pioneers Neogene Therapeutics in 2023 accelerated our work with this new modality. With their expertise, we leverage TCR-Ts to target intracellular proteins and develop personalized therapies engaging specific tumor drivers. We already have three TCR-Ts in clinical development: two targeting common tumor-driver mutations (p53 and KRAS) and a fully individualized, multi-specific TCR-T. Each of these approaches has exciting potential to broaden the scope of cell therapies in solid tumors.

Developing cell therapies for autoimmune, chronic, and rare diseases

Our advancing capabilities in immunology and cell engineering also have applications beyond oncology.

Immune system conditions arise when the carefully programmed immune cells, responsible for protecting the body from bacteria and other threats, malfunction.10 This can cause inappropriate inflammation.

CAR-Ts can reduce inflammation and help transform the therapy for many chronic diseases with an immune component.11 This includes autoimmune conditions driven by loss of immune regulation and chronic kidney disease, which involves considerable inflammation.11 Our ultimate aim is to advance the next generation of cell therapies, with the potential to stop and reverse disease progression in autoimmune conditions, rare diseases, and cancer.

Building on our experience, we are investigating the potential of CAR-T therapies in refractory systemic lupus erythematosus (SLE). In SLE, removing pathogenic B cells can potentially reset and normalize the immune function, changing the outlook for patients with this life-altering and hard-to-treat condition. 

Frank Waldron-LynchVP Immunology Cell Therapy, BioPharmaceuticals, AstraZeneca

Beyond CAR-Ts, our research in immune-mediated diseases aims to stabilize regulatory T cells (Tregs). This T cell subtype can suppress other cells to prevent an overactive immune response.12 This could transform the treatment of a wide range of immune-mediated diseases, including type 1 diabetes, inflammatory bowel disease, and potentially rare genetic conditions.

We aim to stabilize and expand Treg cells in the lab, then reinfuse the new cell population, restoring immune control—potentially a permanent solution. Our partnership with Quell Therapeutics enables us to develop multiple engineered Treg therapies, beginning by targeting type 1 diabetes and inflammatory bowel disease. We aim to bring these potentially curative therapies to the clinic within ten years.

Bringing cell therapies to more patients

To have the most positive impact on patients, we need to overcome barriers that prevent the widespread adoption of cell therapy, such as the complexities of manufacturing and the limited number of specialist treatment centers. We are committed to finding innovative solutions to improve access and scalability of cell therapies.

Scaling our manufacturing and supply

Manufacturing cell therapies requires specialized capabilities, and having the right technology, expertise, and infrastructure is critical for translating research into effective cell therapy medicines. As we accelerate our capacity for next-generation cell therapy discovery, development, and deployment, we have expanded our manufacturing footprint with our recent investment in a state-of-the-art facility in Rockville, Maryland, US, that will focus on manufacturing for critical cancer trials. This is in addition to our facilities in Gaithersburg, Maryland, and Santa Monica, US, and those operated by Gracell (located in China).

One of the most pressing challenges with autologous CAR-T is the lengthy manufacturing timelines, which can lead to suboptimal T cell quality and activity and treatment delays. We are exploring new ways to shorten these timelines. Our acquisition of Gracell brought in their differentiated rapid manufacturing platform, FasTCAR, which aims to deliver less exhausted and potentially more effective CAR-Ts to patients faster.

Off-the-shelf cell therapies

Looking to the future, we are working to engineer cell therapies made from healthy donor blood cells. We aim to develop ‘off-the-shelf’ allogeneic cell therapies to increase the availability and access to these innovative therapies significantly. This would help overcome challenges of scalability, time-intensive personalized manufacturing requirements, and the need for specialist treatment centers. Ultimately, our vision is for a future where physicians can select from libraries of patient-ready therapies that match their disease.

Technology platforms underpinning our pipeline

Our scientists are at the cutting edge of genetic engineering cell therapies, and we are expanding our gene editing toolkit to enable more sophisticated editing of a broader range of therapeutic genes. Our in-house CRISPR gene editing capabilities allow us to selectively modify DNA at specific sites in the genome. This versatile and efficient method targets RNA–DNA interactions and is widely used, offering fast results and easy delivery to cells.13 Complementing our in-house expertise in CRISPR, our collaboration with Cellectis brings an opportunity to harness their differentiated gene-editing expertise with their proprietary TALEN technology. TALEN has the potential for even greater specificity than CRISPR in some circumstances and the ability to target all sites in the genome.14

We are also researching the potential of stem cells for creating more predictive translational models to bridge the gap between pre-clinical and clinical studies. We can direct the differentiation of stem cells into precursors of heart muscle cells and cells that form the ‘scaffold’ of multiple tissues. Using such ‘organoid’ models could give us a far greater understanding of the risks and benefits of new treatments before entering human trials.