Cells as medicines: the promise of cell therapy

Cell therapy is one of the most exciting areas of medical science, with recent years having seen explosive growth in research and development, and even approval of the first cell therapy products. In a series of articles, we’re going to be looking at cell therapy, the technologies which underpin it, challenges to be overcome as it enters mainstream medicine and, because we’re patent attorneys, how intellectual property relating to cellular therapeutics can be protected. Here at Mewburn Ellis we’re proud to work with our many clients who operate in this field at the forefront of medical technology.

Firstly, what is meant by “cell therapy”? Cell therapy encompasses any treatment which involves introducing cells into a patient. Along with gene therapy, cell therapies fall within the special category of “advanced therapy medicinal products” at the European Medicines Agency (EMA) and “cellular and gene therapy products” at the FDA. We will be publishing a related series of articles on gene therapy, as part of our focus on advanced therapeutics here at Mewburn Ellis.

Cell therapy has particular potential for two branches of medicine: cellular immunotherapy and regenerative medicine.

Cellular Immunotherapy

Cellular immunotherapy involves administration of living immune cells into a patient in order to fight a disease suffered by the patient. To date, cellular immunotherapy has been used almost exclusively for cancer treatment, but has potential in several other conditions too, such as autoimmune disease.

Most cellular immunotherapy products rely on modification of natural immune cells to target them against diseased cells. Modern genetic engineering techniques enable expression of receptors which recognise proteins expressed by the target cells, resulting in killing of the target cells by the modified immune cells. It is hoped that in the future, cancer will become broadly treatable by reprogramming patients’ immune systems to target their specific cancers.

Current picture

Although a variety of design options exist for directing immune cells against particular targets, the most clinically advanced approach is chimeric antigen receptor (CAR) cell therapy.

A CAR is a protein which recognises and binds to another protein (an antigen) on a different cell. Immune cells, such as T cells, can be modified outside or inside the body to express a CAR which recognises a protein on a diseased cell, such as a cancer cell, directing the immune cell against the diseased cells. All cellular immunotherapies approved to date rely on expression of CARs by T cells (an approach known as CAR-T therapy) but therapies based on natural killer (NK) cells and other types of immune cells are under development (such as regulatory T cells (Tregs)).

The first FDA approval for a CAR-T therapy was in 2017, when Novartis’s Kymriah (which recognises the B cell marker CD19) was authorised for B cell precursor acute lymphoblastic leukaemia (ALL). Since then, Kymriah has been joined by five other approved CAR-T therapies: Kite Pharma/Gilead’s Yescarta and Tecartus, Bristol Myers Squibb’s Breyanzi (all of which target CD19), Bristol Myers Squibb’s Abecma and Janssen’s Carvykti (which both target B cell maturation antigen (BCMA)). The anti-CD19 CAR-T therapies have been approved for treating various lymphomas, while the anti-BCMA CAR-T therapies have been approved for treating myeloma. These approved CAR-T therapies have provided an additional option for patients who did not respond to existing therapies, enabling treatment of previously untreatable cancers.

All the approved CAR-T therapies use autologous T cells, meaning the patient’s own T cells are isolated, modified to express the CAR and then reintroduced back into them. Use of autologous cells is advantageous as they are tissue-matched to the patient.

Current Limitations and Future Perspectives

At present, all approved cellular immunotherapies are limited to treating B cell malignancies and target proteins expressed specifically on the surface of B cells.

Existing CARs use binding domains derived from antibodies, which are only able to recognise cell surface proteins. Suitable targets for CARs should either be expressed specifically on diseased cells (and not healthy cells), or be expressed only on a particular, non-essential cell type. Targeting of B cell surface markers does not discriminate between healthy and diseased B cells, and so leads to B cell aplasia (i.e. B cell depletion due to their destruction by CAR-T cells), but this is medically tolerable and other cell types are largely unaffected. Few other suitable targets for CARs have been identified though.

To address this limitation work is ongoing to develop cellular therapies reliant on T cell receptors (TCRs). TCRs recognise intracellular proteins, as well as extracellular ones, which hugely expands the array of proteins (and therefore cell types and cancers) which can be targeted. A promising approach is the targeting of neoantigens, peptides generated as a result of mutations in cancer cells, which are not produced by healthy cells.

More challenging will be developing cellular therapies for solid cancers, rather than disseminated cancers such as lymphomas and leukaemias. The tumour microenvironment, including an extracellular matrix, blocks T cell infiltration of solid tumours, and is also heavily immunosuppressive, thus inhibiting the activity of those T cells which do make it inside. Work is ongoing to engineer T cells capable of withstanding the immunosuppressive effects of the tumour microenvironment, and to improve tumour infiltration. It has also been proposed that NK cells, or even macrophages, may be more effective than T cells in treating solid tumours[i],[ii].

Further challenges with existing CAR-T therapies are their high cost (hundreds of thousands of dollars per treatment) and complexity of manufacture, due to the personalised nature of autologous therapies.

One way that costs could be substantially reduced would be to turn to off-the-shelf, allogeneic immune cells. Use of allogeneic T cells is likely to be challenging, primarily due to the risk of graft-versus-host disease (GvHD), which results from the engrafted immune cells attacking the patient’s own tissues. However, NK cells do not appear to cause GvHD and so offer a promising off-the-shelf option.

Whichever allogeneic cells are pursued for therapy, graft rejection is likely to pose a challenge, with administered cells likely to be rapidly depleted by the patient’s immune system. This may necessitate repeated administration of the therapeutic cells, whereas existing autologous CAR-T cells generally require only a single dose. To avoid this, work is ongoing to develop non-immunogenic cells capable of avoiding the host immune system.

Overall, the future of cellular immunotherapy is very exciting. Although there are several challenges to overcome before it can be considered a mainstream therapy, the rapid progress in the field to date suggests these will not be insurmountable.

Regenerative Medicine

Regenerative medicine refers to therapies which aim to replace or repair damaged or diseased cells and tissues in order to restore normal function. Because of their ability to differentiate into other cell types, stem cells have high potential for use in regenerative medicine. Where a particular type of cell is damaged or dead and needs replacing, stem cells can be induced to differentiate into that cell type and are then introduced into the patient.

Stem Cell Types

Stem cells used in medicine can be autologous or allogeneic. The advantage of using autologous cells is that they are inherently tissue-matched to the patient, avoiding rejection of the stem cells and GvHD, but it can be challenging to obtain healthy cells from an ill patient. The risk of using allogeneic cells is that a degree of tissue mismatch is common, which can lead to graft rejection and/or GvHD. However, use of allogeneic cells also has benefits. In the case of blood cancers, allogeneic immune cells may recognise and destroy cancer cells where the patient’s own immune system has not.

Safety Issues

One of the major challenges for stem cell therapies is safety. If the cells are not tissue-matched to the patient, there is a risk of graft rejection. Like when a transplanted organ is rejected, this is caused by the patient’s immune system attacking the introduced cells. Another serious danger, particularly associated with bone marrow transplants, is GvHD.

Various approaches are being pursued to address these issues. Graft rejection can be avoided by using cells which do not induce an immune response, and is not a risk in immune-privileged spaces such as the eye, which is one reason that ocular conditions have seen particular interest as targets for early stem cell therapies.

Current Picture

The most common form of stem cell therapy is bone marrow transplant, now a well-established procedure, but a small number of more advanced stem cell therapies have also entered the clinic. The first stem cell therapeutic approved in the EU was Holoclar®, which received marketing authorisation in 2015 for treatment of the rare eye condition limbal stem cell deficiency (LSCD). Produced by the Italian pharmaceutical company Chiesi Farmaceutici, a graft of autologous corneal epithelial cells generated from limbal stem cells isolated from the patient’s unaffected eye is transplanted into the diseased eye, resulting in corneal regeneration[iii]

Challenges in bringing stem cell therapies to market include ensuring they are sufficiently safe, developing protocols for differentiation of pluripotent stem cells (which have the potential to form any type of cell in the body) into specific target cell types, and their cost of production, particularly for personalised therapies (e.g. autologous therapies such as Holoclar®).

Nonetheless, there has been (and continues to be) substantial investment in stem cell therapies in recent years and many clinical trials are ongoing. We can expect many more stem cell therapies to receive approval in the coming years.

Future Perspectives

Stem cell treatments are being explored in numerous fields, from diabetes to spinal cord injuries, wherever disease is caused by tissue damage or loss. While most stem cell therapies are currently at an early stage, and clinical results have been mixed, the overall picture is hugely exciting with tremendous progress having been made in the last 10 years. Stem cell therapies have the potential to transform the regenerative medicine field in the coming years and decades.

IP Considerations

Patent protection is as important for cellular therapies as for traditional pharmaceutical products. Patentable inventions can be found in many aspects of cellular therapies. For immunotherapies this tends to be relatively straightforward, as they often employ cells that have been modified to express a receptor. Protection can thus be obtained for specific receptors (such as CARs and TCRs) and cells expressing them. Protection can also be obtained for cells with other modifications to enhance their utility, such as modifications to avoid host rejection or to improve tumour infiltration.

Protection for regenerative medicine products can be harder to obtain, as many such products are designed to mimic natural cells or tissues. If a difference can be demonstrated between a therapeutic, stem cell-derived product and a natural product, it may be possible to patent the product itself. Otherwise, it may be more effective to patent the use of such products in methods of treatment.

For all types of cellular therapies, supporting technologies such as methods or media for cell production or expansion can be as important as the therapeutics themselves, and such supporting technologies can also form the basis of important patent rights. Opportunities and challenges relating to patenting of cell therapy technology will be looked at in more detail in future articles.


Cellular therapy is an exciting and fast-moving area of medical science, and we’ll be looking in more detail at several of the technical, regulatory and IP aspects of the technology in a series of blogs to be published over the coming months. If you’d like to discuss any issues relating to patenting cell therapy technology, we’d love to hear from you.

[i] Wrona et al., International Journal of Molecular Sciences 22: 5899, 2021

[ii] Pan et al., Journal of Experimental and Clinical Cancer Research 41: 119, 2022

[iii] Pellegrini et al., Stem Cells Translational Medicine 7(1): 146-154, 2018