Cell therapy involves the delivery of therapeutic cells into a patient to treat disease or repair tissue
Cell therapy spans multiple therapeutic areas including regenerative medicine, immunotherapy and cancer therapy
Cell therapy dates back to 1889 when Charles-Édouard Brown-Séquard attempted to suppress the effects of ageing using injections of animal tissue extracts.
Currently, most cell therapies are in early stages of development (phase 1/2 clinical trials), with a few exceptions being bone marrow/stem cell transplants, liver cell transplants or approved for specific indications such as CAR-T cell therapies for some blood cancers.
Many different types of cells can be used as part of a therapy or treatment for a variety of diseases and conditions including stem cells, skeletal muscle stem cells, mesenchymal stem cells, lymphocytes, dendritic cells, and pancreatic islet cells.
These cells can come from the patient receiving the therapy (called autologous) or from a donor (allogeneic).
Potential applications of cell therapies include treating cancers and autoimmune disease as well as urinary problems, infectious disease, rebuilding damaged cartilage in joints, repairing spinal cord injuries, improving a weakened immune system, and helping patients with neurological disorders.
Immunotherapy, CAR-T cell therapy
One form of cell therapy that has gained much attention in recent years is immunotherapy, which involves harnessing a patient’s own immune system to fight disease.
In the context of immunotherapy, immune cells are isolated from a patient’s blood and, in most cases, genetically modified to elicit specificity to the target tissue. The cells are then expanded into large numbers for subsequent transfer into the patient. Various immune cells may be utilised.
For example, T cells (key cells of the immune system) can be genetically engineered to recognise specific targets expressed by cancer cells in a process known as Chimeric Antigen Receptor (CAR) engineering, producing CAR-T cells.
In May 2022, doctors in the US declared 17-year-old Emily Whitehead ‘cured’ with a CAR-T therapy she received in 2012 for her otherwise untreatable acute lymphoblastic leukaemia (ALL).
After Emily remained cancer free for a decade, her doctors were satisfied they could use the word ‘cure’, something that is rarely, if ever, used in the world of cancer medicine.
There are now six CAR-T cell therapies (all to treat blood cancers) that have been approved for use by the US Food & Drug Administration (FDA), with two of these approved in Australia.
There are currently hundreds of CAR-T cell products in development around the world, with many in clinical trials.
Stem cell therapy
Stem cell therapy (also known as regenerative medicine) is another type of cell therapy that holds significant potential in treating disease.
Stem cells are cells in the body that are able to self-renew and are ‘unspecialised’ – meaning that under certain conditions they can form any type of cell in the body. No other cell in the body has the natural ability to generate new cell types.
There are two main types of stem cells. Embryonic stem cells (derived from early-stage embryos) are considered ‘pluripotent’ in that they can form any type of cell. On the other hand, adult stem cells (found in fully developed tissues) are more limited in the types of cells they can form. Scientists have also been able to generate induced pluripotent stem cells (iPSCs), whereby cells within the body such as skin cells or fibroblasts, can be reprogrammed to be ‘unspecialised’ again and hence under the right conditions, can become any cell in the body.
Currently the only FDA-approved stem cell therapy is hematopoietic (blood) stem cell transplantation, which is used to treat disorders of the blood and immune system.
Much research is currently being done to investigate further use of stem cells to repair or replace diseased tissues and organs in order to treat a wide range of diseases including type 1 diabetes, Parkinson's disease, Alzheimer's disease, heart disease, stroke and also to treat spinal cord injuries, burns, cancer and osteoarthritis.
Scaffold-based cell therapies
Scaffold-based cellular products are engineered technologies that deliver different cell types seeded within 3D biocompatible tissue analogs.
Traditionally, scaffold-based cellular products use biodegradable natural or synthetic polymers with sophisticated porous networks through which oxygen, nutrients and metabolites can be exchanged.
Current scaffold-based cellular products with FDA approval are used for the treatment of diabetic foot ulcers (e.g., Apligraf®, Dermagraft®), burns (OrCel®), and mucogingival conditions (GINTUIT).
Scaffold-free cellular products are tissue analogs that are densely populated with cells carried and protected by their secreted, tissue-specific extracellular matrix (ECM).
This biotechnology allows for the control of cell culture and growth and the deposition of ECM and the formation of cell sheets that adhere to biological surfaces.
An example of commercially available, FDA-approved scaffold-free cellular products is Epicel® (cultured epidermal autografts) – a petrolatum gauze composed of sheets of cells to treat deep burns.
REFERENCE: Abed El-Hakim El-Kadiry, Mouth Rafei & Riam Shammaa (2021). Cell Therapy: Types, Regulation, and Clinical Benefits in Front. Med., 22 Nov 2021, Sec. Gene and Cell Therapy https://doi.org/10.3389/fmed.2021.756029
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