Harnessing the power of cell therapy

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Overview

Using cell therapy to halt and reverse disease, restore damaged organs, and, ultimately, cure many life-threatening conditions is now a realistic goal for AstraZeneca scientists at the cutting edge of regenerative medicine. Important advances in understanding of disease biology and major innovations in gene editing, protein engineering and cell culture technology have created a highly fertile scientific environment in which cell therapy research is flourishing.

In the BioPharmaceutical R&D organisation, pre-clinical research has already shown that cell therapy can be used to replace damaged heart muscle and improve heart function. For chronic kidney disease (CKD), we are investigating the potential of cell therapy to repair diseased blood vessels and improve blood flow to damaged kidney tissue, as well as the use of kidney organoids to regenerate kidney tissue. In autoimmune and inflammatory diseases, we are exploring the possibility that cell therapy may help restore the balance of immune cells so that they no longer attack healthy tissue in conditions such as systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD). Advances in our understanding of the immune system continue to also inform the development of new therapies across a range of tumour types in oncology.


We can now talk about cure because we are seeing science that has the potential to reverse disease, repair and regenerate tissue, making cure a very real possibility. It’s why we as scientists working in medicine – cure has always been our ultimate goal.

Johan Hyllner Senior Director and Head of Cell Therapy, BioPharmaceuticals R&D

Our vision for cell therapy


As an early innovator in cell therapy, AstraZeneca is now investigating the potential of this exciting technology across a broad range of serious diseases affecting almost every part of the body.

Our skills in directing differentiation of multi-purpose, pluripotent stem cells into precursors of heart muscle cells, and cells that form the ‘scaffold’ of multiple tissues, is opening the door to novel therapies for heart failure, kidney and liver diseases.

In Immunology, research aimed at stabilising regulatory T cells to prevent overactive immune responses has potential in the treatment of a wide range of immune-mediated diseases.

Our goal is to develop ‘off-the-shelf’ therapies that can be given to any patient.



Repairing blood vessels in damaged kidneys


Repairing or replacing damaged kidney tissue has the potential to reverse and cure life threatening CKD and the associated life-changing consequences of dialysis and the distressing wait for a transplant.

At AstraZeneca, we are focused on regenerating the kidney as well as improving the distribution of blood and the supply of oxygen to kidney, and we have stem cell approaches focused on these areas. With our expertise in production of miniature organs (organoids) for testing new drug modalities, we are also exploring the tantalising prospect of growing kidney organoids as a therapy option for CKD – an approach arousing considerable interest among our researchers committed to improving the outlook for patients with CKD.1





In five to 10 years’ time I am very hopeful there will be cell therapies available to patients with chronic kidney disease that will enable clinicians to say, “you’ve regained kidney function”. That would be a massive achievement. It’s ambitious and there will be hurdles but there’s a lot of momentum in the research community.

Kevin Woollard Associate Director, Renal Bioscience

New muscle for failing hearts


Up to 1 billion heart muscle cells may die as a result of reduced blood supply during a heart attack.4 This can lead to debilitating and often fatal heart failure.

Researchers in BioPharmaceuticals R&D, in collaboration with Swedish biotech company, Procella Therapeutics and the Karolinska Institute, are determined to change that.

In pre-clinical research, we have injected millions of cells – human ventricular progenitor (HVP) cells  – that are capable of forming new cardiac tissue. In the laboratory, we have seen these HVP cells  develop into beating ventricular cardiomyocytes like those in a healthy heart, leading to improved cardiac function.5

Our collaborators have also reported encouraging anti-fibrotic activity after HVP injections.6 This is important as scar tissue arising from fibrotic changes is typically seen after a heart attack, and reduces normal heart function.

We plan to fully investigate formation of ventricular cardiomyocytes following HVP cell therapy. We want to know how these cells integrate with muscle cells already in the heart, and how they affect tissue regeneration and cardiac function. 



Our ambition is to form new cardiac tissue via remuscularisation of the heart so that we can cure patients with heart failure.

Karin Jennbacken Associate Director Cardiovascular Bioscience and Project Leader for HVP cell therapy project

Working together, we are developing the processes that will ultimately enable the cost-efficient, large-scale manufacture of ventricular progenitor cells to treat thousands of patients with heart failure.

Raghavan Venkat VP and Senior Director

Stabilising T cells to combat autoimmune diseases





Re-balancing the immune system in people whose immune cells mistakenly attack other cells in their body has great potential for innovative, long term treatments for a wide range of immune-mediated diseases such as SLE, IBD and rheumatoid arthritis.

A major focus of our immune cell therapy research at AstraZeneca are regulatory cells, such as regulatory T (Treg) cells, which act as ‘natural brakes’ in the immune system and control the activity of other immune cells. In immune-mediated diseases, Treg cells are outnumbered or lose control, shifting the balance towards destructive immune cells that attack healthy tissue.

As part of our research into novel treatments for patients with immune-mediated diseases, we will investigate how to effectively expand and stabilise regulatory cells in the laboratory so that when they are reinfused into patients, they take back control and prevent the destructive effects of other immune cells.7 

Off-the-shelf functionalised regulatory T cells are the Holy Grail for scientists working on cell therapy for patients with autoimmune diseases. We have a long way to go but, within the next five to 10 years, we hope to see next generation therapies moving into clinical trials of patients with immune-mediated diseases where there is currently a great unmet need.

Tatiana Ort Head of Bioscience Immunology

Using cutting-edge technology


Essential to the important advances already seen in cell therapy at AstraZeneca is an array of cutting-edge technologies. These include gene editing to create ‘universal cells’ that can be given to any patient, and antibodies to target our cell therapies where they are needed most.

Essential to the important advances already seen in cell therapy at AstraZeneca is an array of cutting-edge technologies. These include gene editing to create ‘universal cells’ that can be given to any patient, and antibodies to target our cell therapies where they are needed most.

In patients with heart or kidney failure, universal cells offer the potential for ‘off the shelf’ cell therapy without the need for immunosuppressant drugs to prevent rejection. In Treg therapy for autoimmune diseases, infusions of universal cells could replace the need to extract T cells from each patient’s blood, process and reinfuse them.

To enable our cell therapies to reach the precise areas in the body where they are needed, we will attach antibodies that recognise target tissues and can guide our cell therapies into position. There is also the potential to equip cell therapies with ‘self-destruct’ switches so that if they are no longer needed they can be removed.


With the help of gene editing, the field of cell therapy is now moving ahead at incredible speed and, over the next 10 years, I think we can expect to see treatment making a real difference to patients

Yasuhiro Ikeda Director, Cell Therapeutics Technology



Future directions


Working at the forefront of cell therapy research, we are rapidly extending our capacity and capabilities and recruiting scientists with relevant expertise, to join us in our new state-of-the-art laboratories in Gothenburg, Sweden, Cambridge, UK and Gaithersburg, US research facilities.

As well as our highly successful research collaboration with Procella, we are in active discussions with potential academic and commercial partners to address key challenges of cell therapy and drive progress. We also operate highly successful joint post-doctoral programmes in cell therapy with leading academic institutions including the University of Cambridge and Imperial College London.

We are proud of our progress, prepared for the challenges that lie ahead, and confident that, in the next five to 10 years, cell therapy will help improve the outlook for patients with some of today’s most serious and life limiting diseases. 

At AstraZeneca, the rapidly expanding cell therapy team of scientists, clinicians, regulatory and other experts is working across all our priority therapy areas and building exciting collaborations with colleagues at leading scientific and medical institutions, and with commercial partners around the world.

We are welcoming 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

1. van den Berg CW  et al. In vivo assessment of size-selective glomerular sieving in transplanted human induced pluripotent stem cell–derived kidney organoids. J Am Soc Nephrol 2020; 31: 921-929.

2. Jager KJ et al. A single number for advocacy and communication—worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803-5.

3. Bikbov B et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study. Lancet. 2017;395(10225):709–33

4. Shadrin IY et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat Commun. 2017 Nov 28;8(1):1825. doi: 10.1038/s41467-017-01946-x.

5. Foo KS et al. Human ISL1 + ventricular progenitors self-assemble into an in vivo functional heart patch and preserve cardiac function post infarction. Mol Ther. 2018; 5;26(7):1644-1659.

6. Schneider C et al. Primate heart regeneration via migration and fibroblast repulsion by human heart progenitors. bioRxiv. 2020. doi: https://doi.org/10.1101/2020.07.03.183798

7. Ding M et al. A phenotypic screening approach using human Treg cells identified regulators of forkhead box p3 expression. ACS Chem. Biol. 2019, 14, 543−553.



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Veeva ID: Z4-34011

Date of Prep: May 2021