The development of TAK-940 is part of a broader collaboration with MSKCC.
The product consists of autologous T cells that have been genetically modified to express a CAR targeting the TAA CD19, linked to the costimulatory intracellular signaling domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta; CD28z), with potential immunostimulating and antineoplastic activities
Mechanism of Action1-2
- CD19 1xx CAR T cells specifically recognize and bind to CD19-expressing tumor cells (expressed in B cell lineage malignancies), resulting in T cell-mediated tumor cell lysis
- CD28 and CD3zeta provide co-stimulatory activity and may enhance the cytotoxic effect and anti-tumor activity of CAR T cells
- The CD19 1xx CAR T cells include a 1928zeta mutant, 1xx, which contains one instead of all three immunoreceptor tyrosine-based activation motifs. This characteristic may help prevent counterproductive T-cell differentiation and exhaustion.
CAR, chimeric antigen receptor; CD, cluster of differentiation; MSKCC, Memorial Sloan Kettering Cancer Center; TAA, tumor-associated antigen; TCR, T-cell receptorTAK-940 is also referred to as 1928ζ 1XX
A Phase I Study of CD19-Targeted 19(T2)28z1xx Chimeric Antigen Receptor (CAR) Modified T Cells in Adult Patients With Relapsed or Refractory B-cell Malignancies
1. Takeda Press Release. (Jan 3, 2019). Takeda Announces Multiple Cell Therapy Collaborations to Advance the Company’s Novel Immuno-Oncology Portfolio. [online] Available at: Web Link Accessed April 2023.
2. Feucht J, Sun J, Eyquem J, et al. Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency [published correction appears in Nat Med. 2019 Mar;25(3):530]. Nat Med. 2019;25(1):82-88. doi:10.1038/s41591-018-0290-5
*In collaboration with Memorial Sloan Kettering Cancer Center.
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