The Experts below are selected from a list of 41139 Experts worldwide ranked by ideXlab platform

Rob Pieters - One of the best experts on this subject based on the ideXlab platform.

Ronald W Stam - One of the best experts on this subject based on the ideXlab platform.

Stephen E Sallan - One of the best experts on this subject based on the ideXlab platform.

Marina Konopleva - One of the best experts on this subject based on the ideXlab platform.

  • cd123 expression patterns and selective targeting with a cd123 targeted antibody drug conjugate imgn632 in Acute Lymphoblastic Leukemia
    Haematologica, 2019
    Co-Authors: Evgeniya Angelova, Charlene Audette, Yelena Kovtun, Naval Daver, Sa A Wang, Sherry Pierce, Sergej Konoplev, Haitham Khogeer, Jeffrey L Jorgensen, Marina Konopleva
    Abstract:

    The potential of CD123-targeted therapies in Acute Lymphoblastic Leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of patients with Acute Lymphoblastic Leukemia/lymphoma and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B Acute Lymphoblastic Leukemia/lymphoma cell lines and primary B Acute Lymphoblastic Leukemia/lymphoma blasts. The study cohort (n=213) included 183 patients with B Acute Lymphoblastic Leukemia/lymphoma and 30 with T Acute Lymphoblastic Leukemia/lymphoma. CD123 expression was more prevalent in B Acute Lymphoblastic Leukemia/lymphoma than in T Acute Lymphoblastic Leukemia/lymphoma (164/183, 89.6% versus 13/30, 43.3%; P<0.0001), and within B Acute Lymphoblastic Leukemia/lymphoma CD123 expression was more prevalent in Philadelphia chromosome-positive patients than in Philadelphia chromosome-negative patients (96.6% versus 86.3%; P=0.033). In T Acute Lymphoblastic Leukemia/lymphoma, 12/13 (92.3%) patients with CD123-positive blasts had either early T precursor (ETP) or early non-ETP immunophenotype. IMGN632 was highly cytotoxic to B Acute Lymphoblastic Leukemia/lymphoma cell lines, with half maximal inhibitory concentrations (IC50) between 0.6 and 20 pM. In five of eight patients' samples, low picomolar concentrations of IMGN632 eliminated more than 90% of the B Acute Lymphoblastic Leukemia/lymphoma blast population, sparing normal lymphocytes. In conclusion, CD123 expression is prevalent across Acute Lymphoblastic Leukemia/lymphoma subtypes, and the CD123-targeted antibody-drug conjugate IMGN632 demonstrates promising selective activity in preclinical models of B Acute Lymphoblastic Leukemia/lymphoma.

  • cd123 expression patterns and selective targeting with a cd123 targeted antibody drug conjugate imgn632 in Acute Lymphoblastic Leukemia
    Haematologica, 2019
    Co-Authors: Evgeniya A Angelova, Charlene Audette, Yelena Kovtun, Naval Daver, Sa A Wang, Sherry Pierce, Sergej Konoplev, Haitham Khogeer, Jeffrey L Jorgensen, Marina Konopleva
    Abstract:

    The potential of CD123-targeted therapies in Acute Lymphoblastic Leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of patients with Acute Lymphoblastic Leukemia/lymphoma and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B Acute Lymphoblastic Leukemia/lymphoma cell lines and primary B Acute Lymphoblastic Leukemia/lymphoma blasts. The study cohort (n=213) included 183 patients with B Acute Lymphoblastic Leukemia/lymphoma and 30 with T Acute Lymphoblastic Leukemia/lymphoma. CD123 expression was more prevalent in B Acute Lymphoblastic Leukemia/lymphoma than in T Acute Lymphoblastic Leukemia/lymphoma (164/183, 89.6% versus 13/30, 43.3%; P

Chinghon Pui - One of the best experts on this subject based on the ideXlab platform.