Provided herein are antibodies and antigen-binding fragment thereof targeting CD33, and chimeric antigen receptors (e.g., monovalent CAR, and multivalent CAR including bi-epitope CAR) having one or more anti-CD33 antigen-binding fragments thereof. Further provided are engineered immune effector cells (e.g., T cells) expressing the chimeric antigen receptors and methods of use thereof.

A nucleic acid molecule having a nucleotide sequence encoding a chimeric antigen receptor, where the nucleic acid molecule includes a segment encoding an extracellular domain, a segment encoding a transmembrane domain, and a segment encoding an intracellular domain. The segment encoding the extracellular domain includes a nucleotide sequence encoding an antigen binding region including a light chain variable region and a heavy chain variable region, and at least three codons in a nucleotide sequence encoding framework region 3 of the light chain variable region as defined by the Chothia method are codons encoding acidic amino acid residues.

The present application is directed to methods and compositions that are useful for reducing the number of myeloid-derived suppressor cells (MDSC), tumor associated macrophages (TAM), or both in a subject. The methods include administering an antigen binding protein that binds to an antigen expressed by MDSC and/or TAM, or administering a modified T cell or NK-92 cell that expresses an antigen binding protein that binds to an antigen expressed by MDSC and/or TAM, or a combination of both, to a subject. For example, the antigen binding protein can bind to CD33 expressed by MDSC and/or TAM. The methods and compositions are useful for treating a disease associated with MDSC and/or TAM infiltration into a tissue or tumor.

Provided herein are, inter alia, antibody compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; immune cells bound to compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; humanized OKT3 antibodies; pharmaceutical compositions; and methods for treating cancer, such as multiple myeloma.

The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

The present application provides single-domain antibodies targeting CD33 and constructs thereof, including chimeric receptors, immune effector cell engagers and immunoconjugates. Further provided are engineered immune cells (such as T cells) comprising an anti-CD33 chimeric receptor and optionally a second chimeric receptor targeting a second antigen or epitope. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

Aspects of the present disclosure are directed to borealin-targeting polypeptides, including antibodies, antibody-drug conjugates, antibody fragments, antibody-like molecules, and chimeric receptors. Also disclosed herein are nucleic acids encoding for such borealin-targeting polypeptides and cells comprising such nucleic acids. Described are methods for detection, diagnosis, and treatment of cancer using borealin-targeting polypeptides.

Method for preparing armed immune cells, comprising: isolating a population of CD3.sup.+ immune cells from a human blood sample; and contacting the population of immune cells with a bi-specific antibody specific to CD3 and a tumor associated antigen (TAA) to produce armed immune cells, which display the bi-specific antibody on the cell surface.

An isolated polynucleotide comprising the element of: a promoter element that drives expression of the CC motif ligand 5 (a CCL5 promoter) operatively linked to a polynucleotide encoding a fusion polypeptide comprising the Fc and hinge regions of a human IgG CD44 variant 6 (CD44v6) polypeptide is described.

The present disclosure relates to anti-glyco-cMET antibodies and antigen binding fragments thereof that specifically bind to a cancer-specific glycosylation variant of cMET and related fusion proteins and antibody-drug conjugates, as well as nucleic acids encoding such biomolecules. The present disclosure further relates to use of the antibodies, antigen-binding fragments, fusion proteins, antibody-drug conjugates and nucleic acids for cancer therapy.