Allogeneic chimeric antigen receptor T cells for children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Autor: Franco Locatelli, Francesca del Bufalo, Concetta Quintarelli
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Haematologica, Vol 109, Iss 6 (2024)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2023.284604
Popis: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a breakthrough cancer therapy over the past decade. Remarkable outcomes in B-cell lymphoproliferative disorders and multiple myeloma have been reported in both pivotal trials and real-word studies. Traditionally, the use of a patient’s own (autologous) T cells to manufacture CAR products has been the standard practice. Nevertheless, this approach has some drawbacks, including manufacturing delays, dependence on the functional fitness of the patient’s T cells, which can be compromised by both the disease and prior therapies, and contamination of the product with blasts. A promising alternative is offered by the development of allogeneic CAR-cell products. This approach has the potential to yield more efficient drug products and enables the use of effector cells with negligible alloreactive potential and a significant CAR-independent antitumor activity through their innate receptors (i.e., natural killer cells, γδ T cells and cytokine induced killer cells). In addition, recent advances in genome editing tools offer the potential to overcome the primary challenges associated with allogeneic CAR T-cell products, namely graft-versus-host disease and host allo-rejection, generating universal, off-the-shelf products. In this review, we summarize the current pre-clinical and clinical approaches based on allogeneic CAR T cells, as well as on alternative effector cells, which represent exciting opportunities for multivalent approaches and optimized antitumor activity.
Databáze: Directory of Open Access Journals
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