Process CAR-T cells more efficiently and quickly

CAR-T therapy is a personalized therapy that consists of extracting cells from the patient’s immune system, in this case T cells, and genetically modifying them so that they express a chimeric antigen receptor (CAR) that will allow them to specifically recognize the tumor cells. The modified CAR-T cell population is introduced into the patient and these cells attack the tumor cells.

T-cell therapies have shown unprecedented efficacy in patients with certain B-cell malignancies. However, the process to make these cells is long, taking 20-25 days, and for some patients with very aggressive tumors it is too long. In addition, another of the limitations of the therapy is that the process of amplifying the CAR-T cell population means that they have to divide a lot and very quickly, so the cells when they reach the patient are exhausted, which can compromise the effectiveness”.

Researchers from the Experimental Hematology Group of the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, ​​which is part of the Vall d’Hebron Campus, have participated in the development of a new technology to process CAR-T cells more quickly and effective that could reduce the waiting time of patients to receive treatment.

The achievement is the work of a team that includes Dr. Pere Barba, director of the Advanced Therapies Program at Vall d’Hebron University Hospital, as well as a researcher in the VHIO Experimental Hematology Group. These researchers expose the technical details of their breakthrough in the academic journal Cancer Discovery.

Peter Beard. (Photo: Vall d’Hebron University Hospital Research Institute Foundation)

Traditional production of CAR-T cells requires prolonged cell culture during which the cell population expands. The technology of the new T-charge platform does not require this expansion phase, thus reducing the manufacturing time of the CAR-T itself to less than two days. Also, by not being exposed to cytokines for so long, these cells are not as tired and are more efficient.

With the T-charge platform, door-to-door time (the time that elapses from the patient’s cells are extracted until the final product is delivered to the center where the treatment is performed) can be reduced to 10 days. half.

In preclinical mouse models, researchers have shown that CAR-T cells processed with T-charge technology had more antitumor activity at lower doses than traditionally manufactured CAR-T cells.

The preclinical results have supported the start-up of a phase Y clinical trial in patients with non-Hodgkin B lymphoma (diffuse large cell lymphoma and acute B lymphoblastic leukemia), the preliminary results of which are encouraging: “We have verified that in doses 25 times lower than CAR-T therapy approved for this type of tumors, treatment with T-charge processed CAR-T cells showed promising overall safety and a 75-80% response rate in addition to preserving the T cell phenotype.

“In addition,” adds Barba, “just the fact of reducing the waiting time to receive treatment implies a benefit in the patient’s health status. (Source: Vall d’Hebron University Hospital Research Institute Foundation)