Siglec-6 28z CAR T cells

Siglec-6 28z CAR T cells are an experimental chimeric antigen receptor (CAR) T-cell immunotherapy currently in preclinical development for the treatment of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The therapy involves genetically modifying a patient's T cells to express a CAR that specifically targets sialic acid-binding immunoglobulin-like lectin 6 (Siglec-6), a protein found on AML blasts, AML stem cells, and CLL cells, but notably absent on normal hematopoietic stem and progenitor cells (HSPCs). This expression profile suggests a potential for reduced off-tumor toxicity compared to other AML-targeted CARs. The '28z' designation refers to the use of a CD28 co-stimulatory domain alongside the CD3-zeta signaling domain. The targeting domain is derived from the fully human monoclonal antibody JML-1. While preclinical models have demonstrated potent antileukemia activity, studies have also noted that the 28z construct may have inferior in vivo expansion compared to alternative constructs using 4-1BB co-stimulation.

Other names

Siglec-6-specific CAR T cells (CD28z)JML-1-based Siglec-6 CAR T cellsJML1-based Siglec-6 CAR T cellsJML 1-based Siglec-6 CAR T cells