Provided herein are engineered IL2 polypeptides and fusion proteins thereof. Also provided are methods of modulating an immune response by administering an engineered IL2 polypeptide or a fusion protein thereof. The engineered IL2 polypeptides and fusion proteins thereof demonstrate increased binding to IL2Rβ, decreased binding to IL2Rα, or both.

Antibodies and antigen-binding fragments thereof with high affinity for CD3 and desirable developability profiles are provided, as well as methods for their manufacture and use.

The present disclosure relates to conjugates for delivering therapeutics across the blood brain barrier (BBB) and more particularly to conjugates comprising at least one BBB-shuttling VNAR domain operably linked to a neurotrophic agonist antibody (NAAb), with the conjugate being capable of uptake across a mammalian blood brain barrier (BBB) in a therapeutically-effective amount. These conjugates are useful for treating neurodegenerative diseases, conditions which responds to activation of a neurotrophin receptor as well as for stimulating neuronal survival, growth, repair or regeneration.

The present invention relates, in part, to agents that bind PD-L1 and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the PD-L1 targeting moiety and their use in the treatment of various diseases.

The application provides a multi-specific antibody-like protein having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first binding domain (D1) at the N-terminal, a second binding domain (D2) comprising a light chain moiety, a Fc region, a third binding domain (D3), and a fourth binding domain (D4) at the C-terminal, wherein the light chain moiety comprises a fifth binding domain (D5) covalently attached to the C-terminal, a sixth binding domain (D6) covalently attached to the N-terminal, or both, and wherein the D1, D2, D3, D4, D5 and D6 each has a binding specificity against a tumor antigen, an immune signaling antigen, or a combination thereof.

Provided is application of chimeric antigen receptor (CAR)-modified T (CART) cells in preparing drugs for cancer treatment, the CART cells contain an artificially-introduced costimulatory signal transduction domain, and the CART cell does not contain an artificially-introduced first signal transduction domain.

High-affinity antibodies recognizing CD3 and B Cell Maturation Factor protein (BCMA) are disclosed. Binding sites from humanized anti-CD3 and anti-BCMA antibodies are incorporated into a Fabs-in-Tandem Immunoglobulin format without significant loss of binding affinity, and the resultant bispecific, multivalent binding proteins are able to bind to both CD3 and BCMA simultaneously. Such antibodies, antigen-binding portions thereof, and bispecific FIT-Ig binding proteins are useful for treating cancer.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., ovarian cancer or pancreatic cancer). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to immunomodulatory receptor cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in combination with a therapeutically effective amount of a bispecific antibody that specifically binds Mucin 16 (MUC16) and CD3.

Disclosed herein are anti-mesothelin antibodies and antigen-binding fragments, chimeric antigen receptors (“CARs”) having these anti-mesothelin antibodies and antigen-binding fragments (“mesothelin CARs”) and genetically modified immune effector cells having such mesothelin CARs. Polynucleotides encoding the anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. Compositions comprising anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. The present disclosure also relates to uses of the anti-mesothelin antibodies and antigen-binding fragments and genetically modified immune effector cells having such mesothelin CARs in cancer treatment.

Disclosed are antigen binding polypeptides and antigen binding polypeptide complexes (e.g., antibodies and antigen binding fragments thereof) having certain structural features. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes; chimeric antigen receptors (CARs), cells, pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes.