Abstract: Aspects of the disclosure relate to compositions and methods for treating certain (e.g., CD33-positive) cancers. In some aspects, the disclosure provides antibodies that specifically bind to CD33 protein variants that lack an IgV domain. In some aspects, the disclosure provides adaptable cell engagers (ACEs) and recombinant proteins (e.g., BiTEs) comprising an anti-CD33 antibody of the disclosure and an anti-CD3 antibody. In some embodiments, the disclosure provides methods of treating cancer by administering the antibodies, ACEs, or recombinant proteins (e.g., BiTEs) to a subject in need thereof.

Abstract: Aspects of the disclosure relate to compositions and methods for predicting prognosis and classifying risk of subjects having certain cancers, for example acute myeloid leukemia (AML). In some embodiments, methods described by the disclosure comprise a step of assessing the mRNA expression of certain leukemic stem cell (LSC)-enriched genes in a subject to produce a predictive score for pediatric AML. In some embodiments, methods described by the disclosure comprise a step of assessing the mRNA expression of certain genes of pharmacological relevance for standard chemotherapy consisting of Cytarabine (also known as Ara-C), daunorubicin and etoposide in a subject to produce a predictive score for pediatric AML.

Abstract: Aspects of the invention relate to detecting single nucleotide polymorphisms for CD33 and determining whether a subject is likely to respond to treatment with agents that selectively bind to CD33 based on the genotype of the subject for one or more CD33 single nucleotide polymorphisms.