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

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