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Table 1 Agents used for the targeting of CD123 in leukemic patients

From: CD 123 is a membrane biomarker and a therapeutic target in hematologic malignancies

Agent Efficiency in treatment model Targeting of LSCs Effect on normal Postulated mechanism Clinical studies
SL-401 (human IL-3 conjugated to a truncated diphteria toxin) Induces a pronounced clearing of leukemic cells, including AML blasts, BPDCN tumor cells, MM cells Induces killing of CFU-L. Induces the killing of CD34+/CD38- leukemic cells 40-50% inhibition of CFU-GM Induces the apoptotic killing of cells expressing CD123 Phase I in AMLs and BPDCN. Phase II studies are planned
CSL362 (humanized form of the 7G3 anti-CD123 mAb, IL3 neutralizing) Reduces AML leukemic stem cell homing, engraftment and self-renewal ability and improves the survival of mice, with minimal effect on normal BM cells Inhibits spontaneous and IL3-induced proliferation of CD34+/CD38- leukemic cells. In vivo treatment of xenografted NOD/SCID mice targets LSCs Dose-dependent depletion of PB basophils and plasmacellular dendritic cells, transient decrease of NK cells and no effect on monocytes and HPCs and HSCs. ADCC-facilitated lysis of leukemic CD123+ leukemic cells mediated by NK cells Phase I in AMLs
CD123 CART cells (T cells expressing CD123-specific receptors) Induces an antileukemic effect in nude mice xenografted with human CD123+ AML cells 70-80% inhibition of CFU-L 40-50% inhibition of CFU-GM; 10-20% inhibition of BFU-E. The cytotoxic effect is limited to cells displaying high CD123 expression Antibody-mediated T cell killing of CD123+ leukemic cells. Activation of cytokine production and effector functions of T lymphocytes None