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EHA 2023 | ADCLEC.syn1 CAR: ADGRE2-targeting 28z1XX-CAR and a CLEC12A-targeting CCR in humanized AML models

Relapsed and refractory (R/R) acute myeloid leukemia (AML) represents a large clinical unmet need, with overall five-year survival at around 30%. Cellular therapies have provided clinicians treating B-cell malignancies with a fantastic additional line of therapy, and present a potential opportunity in this space to improve patient outcomes. In this presentation, Sascha Haubner of the Memorial Sloan Kettering Cancer Center, New York, NY, discusses a study comparing the efficacy of a novel combinatorial CAR design, ADCLEC.syn1, to a CD33-targeted CAR in AML models. ADCLEC.syn1 consists of an ADGRE2-targeting 28z1XX-CAR and a CLEC12A-targeting chimeric costimulatory receptor (CCR), providing additional 4-1BB costimulation. The results showed that ADCLEC.syn1 was effective in eliminating CD33-CAR refractory AML in patient-derived xenografts (PDX). These findings highlight the importance of quantitative CAR target profiling in AML and normal tissues to guide CAR design, and prompt additional research into how antigen expression on normal bystander cells may influence CAR efficacy. ADCLEC.syn1 T cells will soon be investigated for R/R AML in a first-in-human Phase I clinical trial at MSKCC (NCT05748197). This press briefing took place at the European Hematology Association (EHA) Congress 2023, held in Frankfurt, Germany.

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