A world-first approval for off-the-shelf cell therapy

We are delighted to learn that this week the European Commission granted the world’s first approval for an allogeneic “off-the-shelf” T-cell immunotherapy1. Market authorisation was granted for Ebvallo (tabelecleucel) for the treatment of a rare blood cancer: Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD). The approval comes just a week after Great Ormond Street Hospital announced that a teenaged patient became the first to receive a different kind of allogeneic CAR T-cell therapy that successfully cured her of T-cell acute lymphoblastic leukaemia2.

The authorisation is specifically for treatment of patients over the age of 2 years, who have received at least one prior therapy. For solid organ transplant patients, the prior therapy includes chemotherapy unless chemotherapy is an inappropriate course. Until now, patients could only access this treatment through participating in clinical trials or via expanded access programs for those with no other treatment options3.

What is “off-the-shelf” cell therapy?

“Off-the-shelf” or “allogeneic” therapies are a type of cellular immunotherapy wherein T cells sourced from healthy donors are stimulated to attack a particular antigen that is present on the cancerous cells, for example EBV, by culturing with a sample of the donor’s immune cells that are infected with EBV. Other types of allogeneic T cells might be engineered to express additional receptors that help recognise and attack cancerous cells. Populations of these primed allogeneic donor cells are then expanded in a bank so that ample supplies are ready for infusion into the patient, where they recognise and kill the cancerous cells. Allogeneic therapies act as a rapid alternative to autologous cell therapies, such as most CAR-T cell therapies, which instead use the patient’s own T cells.

What are the benefits?

A standout benefit of allogeneic cell therapies over autologous cell therapies is the wait time: large banks can be used to culture vast quantities of allogeneic cells, all specific for the same antigen, that are suitable for administration to thousands of patients. Cell culturing in these banks is of course tightly regulated, but in short, the scale-up is highly efficient in terms of cost, labour, materials and time.

Meanwhile, autologous treatment options require harvesting, stimulation and expansion of the patient’s own cells before any treatment course can commence. Such as with CAR-T cell therapy, most autologous cell therapies are further engineered to express receptors to enhance killing capabilities, lengthening the time until treatment is possible.

Challenges and trials

Challenges associated with allogeneic therapies mostly stem from issues regarding immunological tolerance. During culture, donor cells must be shed of their receptors that are unique to each person, such as to avoid being too rapidly eliminated by the patient’s own immune system, or worse, triggering a dangerous graft-versus-host response4. Saying this, a Phase III ALLELE study for Ebvallo demonstrated a favourable risk-benefit profile. Safety profiles also proved consistent with previous trials, with no evidence of a graft-versus-host response5. These data helped Ebvallo gain a positive opinion from the Committee for Medicinal Products for Human Use, prior to approval from the European Commission6.

What’s next?

The news of the first allogeneic cell therapy approval will have been hotly anticipated by other key players in the field. Cancer isn’t the only target for such therapies; autoimmune diseases such as multiple sclerosis are also in innovators’ sights. The coming years will likely be pivotal for cell therapy developers and regulators alike, and we eagerly anticipate the next product ready to be taken “off-the-shelf”!



  1. Kansteiner, Fraiser (2022). Atara makes history with world-first nod for allogeneic T-cell therapy Ebvallo. Fierce Pharma. https://www.fiercepharma.com/pharma/atara-makes-history-world-first-nod-allogeneic-t-cell-therapy-ebvallo/ 

  2. Great Ormond Street Hospital (2022). GOSH researchers develop breakthrough treatment for previously incurable leukaemia. https://www.gosh.org/news/gosh-researchers-develop-breakthrough-treatment-for-previously-incurable-leukaemia/

  3. Smith, J. (2022). Ebvallo approval ushers in off-the-shelf T cell immunotherapies. Labiotech. https://www.labiotech.eu/in-depth/atara-biotherapeutics-ebvallo/ 

  4. Caldwell, K. J., Gottschalk, S., Talleur, A. C. (2021) Allogeneic CAR Cell Therapy – More Than a Pipe Dream. Frontiers in Immunology (11). https://doi.org/10.3389/fimmu.2020.618427 

  5. Atara Biotherapeutics (2022). Atara Biotherapeutics Presents Updated Clinical Data from Pivotal Phase 3 Trial (ALLELE) of Tab-cel® at the 64th American Society of Hematology (ASH) Annual Meeting. https://investors.atarabio.com/news-events/press-releases/detail/299/atara-biotherapeutics-presents-updated-clinical-data-from

  6. Eckford, C. (2022). World’s first approval of an allogeneic T-cell immunotherapy. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/news/177795/worlds-first-approval-of-an-allogeneic-t-cell-immunotherapy/