Dragan Cicic, Chief Medical Officer of Actinium Pharmaceuticals, added, "These latest data from our CD33
targeting program provide yet another validation for our approach of utilizing targeted alpha-emitters in older high risk AML patients, an area of high unmet medical need.
E-cadherin, an adhesion molecule mainly found on the surface of epithelial cells,[11,14] has been demonstrated to play major roles during morphogenesis, in the maintenance of epithelial tissues, and in malignant tumors. It was recently demonstrated by flow cytometric analysis that E-cadherin is transiently expressed on bone marrow erythropoietic cells.[6,17] Double-labeling experiments with anti-E-cadherin antibody revealed coexpression with the molecules glycophorin A and the transferrin receptor, while no coexpression was found with lymphoid (CD2, CD3, CD10, CD19, CD56, and CD62L) and myeloid (CD13, CD33
, and CD41) markers.[6,17] E-cadherin appeared to be strongly expressed on erythroblasts and to decrease during maturation of erythroid precursors.
This would potentially be an important safety advantage compared to other targeted therapies for AML where the target antigen is expressed on normal stem and progenitor cells, such as CD33
The following monoclonal antibodies were used: CD3, CD4, CD5, CD7, CD8, CD10, CD13, CD14, CD19, CD22, CD33
, CD34, CD45, anti-[Kappa], anti-[Lambda], HLA-DR (Becton Dickinson), terminal deoxynucleotidyl transferase (Dako), and intracytoplasmic CD3 and myeloperoxidase (Caltag, Burlingame, Calif).
A panel of monoclonal antibodies was used specific for the following antigens: CD2, CD3, CD4, CD7, CD8, CD10, CD13, CD19, CD33
, CD34, CD38, CD45 (LC, A), CD56, CD64, CD117 (c-kit), HLA-DR, and terminal deoxynucleotidyl transferase (TdT).
(NASDAQ: IMGN) presented data from the ongoing Phase 1 study evaluating single agent IMGN779 in patients with relapsed or refractory adult acute myeloid leukemia whose tumors express CD33
at the 22nd Congress of the European Hematology Association in Madrid, Spain, the company said.
Staining Characteristics of Acute Megakaryotic Leukemia Blasts and Micromegakaryocytes Cytochemistry Immunophenotype (-) Sudan black B (+) Platelet glycoprotein Ib (CD42b) (-) Myeloperoxidase (+) Platelet glycoprotein IIb/ IIIa (CD41) (-) Terminal (+) Platelet glycoprotein IIIa deoxynucleotidyltransferase (CD61) (+) Periodic acid-Schiff, (+) Factor VIII-related antigen acid phosphatase (+/-) Nonspecific esterase (+/-) HLA-DR, CD33
, CD34 (focal, paranuclear)
These antibodies included CD10, HLA-DR (Ia), CD11b, CD15, CD13, CD33
, CD14, and CD45.
In this latest study, the team used blood samples taken from patients and showed that a protein called CD33
is present on the surface of MDSCs** across a wide range of cancers.
VOR33 is designed to produce healthy blood cells that lack the receptor CD33
, thus enabling the targeting of AML cells through the CD33
antigen while avoiding toxicity to the blood and bone marrow.
The expression of characteristic myeloid lineage markers CD13, CD33
and CD117 allows the distinction of AML from other types of leukaemias.4 In the diagnosis of acute leukemia concordance between experienced observers increases from 70 to 99% when morphologic criteria are supplemented by cytochemical and immunophenotypic information.5 Immunophenotyping plays an important role when morphological interpretation is difficult.
Lineage-specific markers, including myeloid (CD13, CD33
, CD117, MPO), monocytic (CD11b, CD14, CD64), megakaryocytic (CD61), B-cell (CD19, CD10, CD20) and T-cell (CD3) antigens, were negative.