The therapies approved to treat various tumors using CAR-T cells are based on the modification in the laboratory of the patient’s own lymphocytes, which delays their administration. Now, a phase 1 clinical trial has used ready-made cells from donors to treat patients with multiple myeloma. The results, which are published in the journal ‘Nature Medicine’, show that allogeneic CAR-T cell therapy, which uses cells from one healthy donorrather than cells from the patient, may be a possible treatment option for patients with multiple myeloma.
CAR-T therapy ( Chimeric Antigen Recetor T-Cell ) is not a medicine to use. It is a ‘living’ drug that is manufactured for each patient with a particular preparation: the cells of the patient’s immune system (T lymphocytes) are extracted, they are genetically modified to make them more potent and selective, and they are reinfused into the patient.
And this was precisely the bottleneck since the manufacture of these CAR-T cells is very time consuming and some patients may experience progression of their disease during this period and need an intermediate form of treatment between the initial collection of cells from the patient and the final infusion of CAR-T cells.
Additionally, some patients may experience progression of their cancer and become ineligible for the infusion, while others may die in the interim.
In this ongoing Phase 1 clinical trial, allogeneic CAR-T cells made from cells harvested from a healthy donor rather than from the patient were used, making them easier to prepare ahead of time, potentially allowing patients to receive faster treatment.
The team at the Memorial Sloan Kettering Cancer Center in New York (USA) of Sham Mailankody engineered T cells donated from a healthy person to be able to recognize the BCMA antigen, which is overexpressed on multiple myeloma cells.
They then combined the cells with an antibody that targets a cell-surface glycoprotein called CD52, which is found on a variety of host immune cell types.
So far, 43 patients have been treated with doses of CAR T cells.
The authors suggest that their data show that treatment is safe.
They indicate that the overall response rate (the percentage of patients whose cancer shrank after treatment) was 55.8%, and among the 24 patients who received high-dose CAR T cells, the response rate was 70, 8%.
They also note that 53.5% of treated patients experienced infection after treatment, with three infection-related deaths.
Luis Álvarez-Vallina, head of the H12O/CNIO Mixed Cancer Immunotherapy Unit, points out to the Science Media Center that the fundamental advantage of this type of allogeneic product is immediacy, since the time elapsed between patient recruitment, lymphodepletion and the infusion of CAR-T cells is for a few days, whereas in autologous CAR-T therapies [con células del propio paciente] the mean time between apheresis and product availability is greater than 30 days, which is too long a period for many refractory patients without other therapeutic options.
In the future, both will have to be used: the patient’s own cells and donor cells.
Álvarez-Vallina acknowledges that this is a first study and it will be necessary to optimize multiple parameters such as dose, administration schedule, etc., but «the results demonstrate the feasibility, safety and efficacy of this allogeneic CAR-T cell therapy in patients with multiple myeloma».
The professor at the University of Pennsylvania, Carl June, father of these innovative treatments that revolutionized cancer treatment, had already acknowledged in an interview with ABC Salud that in the future both will have to be used: the patient’s own cells and cells from a bank. of cells, called universals. “The second ones will be cheaper, but they pose some problems in terms of their long-term safety, something that does not happen with those from the donor itself.”
The authors conclude that their results demonstrate the feasibility and safety of allogeneic CAR T-cell therapy for multiple myeloma.
However, they acknowledge that hWe must wait for the final results of this trial.