Abstract: Humanized, chimeric, murine, and human antibody or antigen binding derivatives thereof that bind to an extracellular domain of interleukin-3 (IL-3) receptor ?-chain (CD123) anti-CD123 monoclonal antibodies are provided. Nucleic acids encoding the antibody or antigen binding derivative thereof that binds to an extracellular domain of interleukin-3 (IL-3) receptor ?-chain (CD123) and expression vectors comprising the nucleic acid are also provided. Bispecific affinity reagents comprising a first binding domain that specifically binds to an extracellular domain of interleukin-3 (IL-3) receptor ?-chain (CD123); and a second binding domain that specifically binds to a therapeutic payload and uses thereof are provided. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized, chimeric, or human anti-CD123 monoclonal antibodies; and cell lines that produce these monoclonal antibodies.

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of human CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: A suite of novel anti-CD33 antibodies is described. The provided antibodies are pan-binders, binding the C2-set Ig-like domain in the presence or absence of the V-set Ig-like domain of CD33; are C2-set specific binders, binding the C2-set Ig-like domain only in the absence of the V-set Ig-like domain of CD33; or are V-set binders, binding the V-set Ig-like domain of CD33. The antibodies provide novel therapeutic and diagnostic tools against CD33-related disorders, such as acute myeloid leukemia (AML).

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: A suite of novel human anti-CD33 antibodies is described. The provided antibodies are pan-binders, binding the C2-set Ig-like domain in the presence or absence of the V-set Ig-like domain of CD33 or are V-set binders, binding the V-set Ig-like domain of CD33. The antibodies provide novel therapeutic and diagnostic tools against CD33-related disorders, such as acute myeloid leukemia (AML).

Abstract: Anti-CD33 antibodies are described. The anti-CD33 antibodies can bind within the V-set Ig-like domain or the C2-set Ig-like domain of CD33. Epitopes on the C2-set Ig-like domain can provide a “pan-binding” site, to which the cognate antibody will bind regardless of whether the CD33 molecule also contains the V-set domain (as in, for example, CD33FL) or not (as in, for example, CD33?E2). Alternative epitopes on the C2-set Ig-like domain are accessible for binding if the V-set domain is absent (e.g., as in CD33?E2). Antibodies that bind an epitope on the C2-set Ig-like domain (whether they exhibit pan or V-set absent binding) are directed at novel therapeutic targets and can increase therapeutic efficacy against CD33-related disorders. Also described are molecules comprising a binding-competent domain from at least one described anti-CD33 antibody, including scFvs, bi-specific antibody molecules, chimeric antigen receptors, and immunoconjugates. Methods of use are also provided.

Abstract: Groups of bi-specific binding domain constructs (BS-BDC) to treat cancer are described. Each BS-BDC in a group targets a cancer antigen epitope and an immune cell activating epitope that is different from the cancer antigen epitope and immune cell activating epitope targeted by another BS-BDC in the group. The different cancer antigen epitopes can be on the same cancer antigen.