There has been a significant shift away from cytotoxic agents, with key mechanisms of action including targeted therapies against CD33, CD123
Cellectis is currently developing three proprietary allogeneic CAR T-cell product candidates in the field of liquid tumors, targeting CD123
in acute myeloid leukemia, as well as CD38 and CS1 for multiple myeloma.
Flow cytometry showed a 96% variable size, clonal B cell population expressing CD10, CD11c, CD19, CD20, CD22, CD45, CD52, CD103, CD123
, BCL2, and Kappa.
Markers that were negative (0%) included CD30 (n = 6), [kappa] light chain (n = 2), [lambda] light chain (n = 2), CD8 (n = 2), CD1a (n = 1), CD2 (n = 1), CD5 (n = 1), CD7 (n = 1), CD15 (n = 1), CD45RO (n = 1), CDw75 (n = 1), CD79a (n = 1), CD123
(n = 1), CD138 (n = 1), PAX5 (n = 1), TCL-1 (n = 1), and anaplastic lymphoma kinase (ALK; n = 1).
The promising drug is an antibody that blocks a receptor called CD123
found on the surface of stem cells at risk of developing into leukemia cells.
The new treatment targets a protein, CD123
, on the surface of cancer stem cells that drive acute myeloid leukemia (AML), which is an aggressive disease with a poor outcome.
Investigation of the normal differentiation pathways of CD34+ precursors as regards the acquisition of MPO, lysozyme, CD64, CD15, or CD123
expression will certainly contribute to a better discrimination among the different myeloid cell lineages (120-122,124,125).
Flow cytometry on the bone marrow revealed a 14% aberrant T-cell population expressing CD2, CD3 (dim), CD4, CD5, CD25, CD45, CD52, and CD123
Immunohistochemistry for CD123
demonstrated an increased number of plasmacytoid dendritic cells (Figure 1).
Immunohhistochemical Marker Cell type CD45 CD21 CD23 CD35 SI00 CDla Langerin Fascin LCH LC (+) (-) (-) (-) (+) (+) (+) only + IDC (+) (-) (-) (-) (+) (-) (-) (+) Macrophage or (+) (-) (-) (-) (+/-) (-) (-) (+/-) histiocyte l/DDC (+) (-) (-) (-) (-/+) (-) (-) (+) pDC (-) (-) (-) (-) (-) (-) (-) (-) FDC (-) (+) (+) (+) (+/-) (-) (-) (+) FRC (+) (-) (-) (-) (-) (-) (-) Cell type Clusterin CD68 CD123
CD163 CD4 FXIIIa TCLI LC (-) (+) (-) (-) (+) (-) (-) IDC (-/+) (+/-) (-) (-) (+) (-) y Macrophage or (-) (+) (-) (+) (+) (-) (-) histiocyte l/DDC (-) (+) (-) (-) (+/-) (+) (-) pDC (-) (+) (+.
Lock and his colleagues exploited the fact that the molecule CD123
is expressed at very high levels on LSCs but not on normal blood cells.
XmAb14045 (CD123xCD3 bispecific antibody): Xencor plans to initiate clinical trials of XmAb14045 targeting CD123
, a target on tumor cells in acute myeloid leukemia, and CD3 in 2016.