^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
DRUG:

CD70-directed CAR-T

i
Other names: CD70-directed CAR-T, CD70 CAR T-cells
Associations
Trials
Company:
Massachusetts General Hospital
Drug class:
CD70-targeted CAR-T immunotherapy
Associations
Trials
over2years
Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia. (PubMed, Cancer Cell)
We then use orthogonal approaches to increase binding on both the tumor and CAR-T cell sides of the immune synapse: a pharmacologic approach (azacitidine) to increase antigen density of CD70 in myeloid tumors, and an engineering approach to stabilize binding of the CAR to CD70. Our CD8 hinge and transmembrane-modified CD70 CAR-T cells are less prone to cleavage, have enhanced binding avidity, and increased expansion, leading to more potent in vivo activity. This enhanced CD70-targeted CAR is a promising candidate for further clinical development.
Journal • CAR T-Cell Therapy
|
CD70 (CD70 Molecule) • CD27 (CD27 Molecule)
|
azacitidine • CD70-directed CAR-T
3years
Rational Chemical and Genetic Modifications Enhance Avidity and Function of CD70-Directed CAR-T-Cells for Myeloid Leukemia (ASH 2021)
The TNF-alpha family member CD70 has emerged as a promising surface target antigen in AML after high complete response rates (CR) were seen in a Phase 1 trial of the CD70 antibody cusatuzumab (Riether et al, Nature Medicine 2020). Our findings demonstrate that natural-ligand binding domains of CARs targeting CD70 in AML can be effective but require mechanisms to overcome surface cleavage. CD70-targeted CARs comprised of a fusion of truncated CD27 to a CD8 hinge and transmembrane domain have promise in patients with AML, with and without combination with azacitidine.
CAR T-Cell Therapy • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CD70 (CD70 Molecule) • CD27 (CD27 Molecule)
|
CD70 expression
|
azacitidine • cusatuzumab (ARGX-110) • CD70-directed CAR-T