CLEC12A-targeting CCR/anti-ADGRE2 CAR T cells ADCLEC.syn1

A preparation of T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the human myeloid-restricted adhesion G protein-coupled receptor E2 (ADGRE2; EGF-like module receptor 2; EMR2; CD312), and a chimeric costimulatory receptor (CCR) targeting C-type lectin domain family 12 member A (CLEC12A, C-type-lectin-like molecule-1; CLL-1; CLL1), with potential immunomodulating and antineoplastic activities. Upon administration, CLEC12A-targeting CCR/anti-ADGRE2 CAR T cells ADCLEC.syn1 target and bind to ADGRE2- and CLEC12A-expressing tumor cells. This induces selective toxicity in tumor cells that express a high level of ADGRE2, and tumor cells that express both ADGRE2 and CLEC12A. ADGRE2 is expressed mainly on myeloid cells and is overexpressed on leukemic stem cells (LSCs) in acute myeloid leukemia (AML). CLEC12A, a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily, is overexpressed on LSCs and plays an important role in disease progression and relapse for myeloid malignancies. ADGRE2 and CLEC12A are highly co-expressed in AML and not in normal tissues. Targeting both ADGRE2 and CLEC12A may improve efficacy and reduce adverse effects.