Current state and next-generation CAR-T cells in multiple myeloma.
Blood Rev
; 54: 100929, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35131139
ABSTRACT
Chimeric antigen receptor T cells (CAR-T cells) have emerged as a potentially transformative new approach to treating hematological malignancies. Ide-cel, an autologous B cell maturation antigen (BCMA) targeting CAR-T cells, has recently been approved to treat multiple myeloma (MM). Here, we review the main clinical trials of CAR-T cells in MM with the most advanced autologous BCMA-directed ide-cel and cilta-cel, the human CARs orva-cel and CT053, the alternative manufacturing process with P-BCMA-101 and bb21217, the dual CAR GC012F and the allogenic BCMA-directed CAR-T cells ALLO-715. In light of those clinical data, we provide an overview of CAR-T cells' main potential resistance mechanisms, including antigen loss, antigen spreading, anti-CAR antibodies, CAR-T cell exhaustion, and the emergence of a non-permissive microenvironment. Finally, we describe the principal area of research to build the next generation of CAR-T cells, with armored-, gated- or commuting-CARs, CARs associated with knock out of specific genes, and CAR-T cells made from γδT cells or NK cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígeno de Maturação de Linfócitos B
/
Mieloma Múltiplo
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article