Food and Drug Administration (FDA) accepted our first Investigational New Drug (IND) application to initiate a multi-center Phase 1/2 clinical trial of MB-102 (CD123
CAR T) in acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN) and high-risk myelodysplastic syndrome (MDS).'
is widely expressed on bone marrow cells of patients with myelodysplastic syndrome and hematologic malignancies, including in 75-89% of AML patients and over 90% in BPDCN patients.
However, it is now known to be derived from the recently recognized subtype of dendritic cells named plasmacytoid dendritic cells (PDC) which are characterized by expression of CD4, CD56, and more PDC-specific markers such as CD123
Mustang Bio was granted orphan drug designation for MB-102 (CD123
CAR T) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and incurable blood cancer with a median survival of less than 18 months and no standard of care.
The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123
, CD4, and CD56.
Eight-color MFC was performed in all patients as a routine clinical test on BM samples that were obtained as part of baseline assessment at the time of diagnosis, the end of the first and second courses of chemotherapy, as well as pre-HSCT., A panel of eight antibody combinations that recognize CD7, CD11b, CD13, CD14, CD16, CD19, CD33, CD34, CD38, CD41, CD45, CD56, CD61, CD64, CD71, CD117, CD123
, and HLA-DR was used for MRD detection, and 0.2-1 million events per tube were acquired on a Fluorescence activated cell sorter (FACS Canto II) (BD Co., USA).
Plasmacytoid dendritic cells expressing CD123
are also seen.
Silva et al., "Langerhans cells (CD1a and CD207), dermal dendrocytes (FXIIIa) and plasmacytoid dendritic cells (CD123
) in skin lesions of leprosy patients," Microbial Pathogenesis, vol.
Antibodies against CD markers (CD3, CD4, CD14, CD19, CD16, CD56, CD20, CD123
, HLA-DR, CD11c, and CD38) were purchased from the eBioscience company (San Diego, CA, USA).
The following monoclonal antibodies were added to the fresh blood, which was cultured at room temperature for 2h: Lineage-1, fluorescein isothiocyanate (FITC; BD Biosciences, San Jose, CA, USA); HLA-DR, Per-CP (BD Biosciences); CD11c, FITC (BD Biosciences); CD11c, PE (BD Biosciences); and CD123
, PE (BD Biosciences).
(PCD) dendritic cells have tolerogenic effects, and they gradually increase in number during the rejection-free post-transplant period.
, the plasmacytoid dendritic cell phenotypic marker is abundant in leprosy type 1 reaction.