An antibody or an antigen-binding fragment thereof capable of specifically recognizing IL-11. The antibody includes heavy chain variable region CDRs as shown in SEQ ID NOs: 4-6, light chain variable region CDRs as shown in SEQ ID NOs: 37-39, heavy chain framework regions as shown in SEQ ID NOs: 67-70, and light chain framework regions as shown in SEQ ID NOs: 71-74, respectively. The antibody has low immunogenicity and can specifically target and bind to IL-11, so as to block binding of IL-11 to an IL-11 receptor.

Provided are anti-IL-36R antibodies or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same and the uses thereof.

Provided are modified cells and methods for their use in treating cancer. The cells are modified to express and secrete a Bi-specific T cell engager (BiTE) that includes a segment that specifically binds to human Folate Receptor alpha (FR) and a segment that that specifically binds to human CD3, such as CD3e. The modified cells can be T cells. Methods for producing the modified cells are also provided.

Disclosed herein are recombinant polypeptides and recombinant nucleic acids encoding the same. According to some embodiments of the present disclosure, the recombinant polypeptide comprises a first bi-functional domain, and a first single-chain fragment variable (scFv) or a peptide linked to the N-terminus of the first bi-functional domain. Optionally, the recombinant polypeptide further comprises a second scFv linked to the N-terminus of the first scFv or peptide. Also disclosed herein are methods of treating cancers by using the immune cells expressing the recombinant polypeptides.

Chemically induced dimerizers (AbCIDs) have emerged as one of the most powerful tools to artificially regulate signaling pathways in cells; however, no facile method to identify or design these systems currently exists. The present invention provides a methodology to rapidly generate antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule-protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. Success of this strategy is demonstrated by generating ten chemically-inducible antibodies against the BCL-xL/ABT-737 complex. Three of the antibodies are highly selective for the BCL-xL/ABT-737 complex over BCL-xL alone. Two exemplary important cellular applications of AbCIDs are demonstrated by applying them intracellularly to induce CRISPRa-mediated gene expression and extracellularly to regulate CAR T-cell activation with the small molecule, ABT-737. ABT-737 is not toxic at the concentrations used to activate AbCIDs in cells. AbCIDs provided by this invention are new and orthogonal AbCIDs, expanding the limited toolbox of available CIDs.

Provided herein are compositions and methods for providing long-term and sustained CAR T cell efficacy. For example, expression cassettes that encode both a GPC2-targeting chimeric antigen receptor and a bispecific innate immune cell engager binding both GD2 on tumor cells and CD16A on natural killers (NK) and macrophages are provided. In addition, T cells that both expression a GPC2-targeting chimeric antigen receptor on their surface and secrete a bispecific innate immune cell engager binding both GD2 on tumor cells and CD16A on natural killers (NK) and macrophages are provided.

Engineered T cell receptor (TCR) complex and methods of using same are provided. Accordingly, there is provided a TCR comprising a TCR alpha polypeptide and a TCR beta polypeptide, wherein the TCR is devoid of a binding domain, wherein the TCR alpha and beta polypeptides comprise amino acid modifications enabling presentation of the TCR as a TCR complex on a surface of a T cell expressing same. Also provided are polynucleotides encoding the TCR. T cells expressing the TCR complex and methods of using same.

Provided is a membrane surface protein containing a GPI anchor region. Specifically, provided are a fusion protein comprising a functional domain and a GPI anchor region, and the use thereof. The fusion protein can effectively activate and proliferate immune cells, and improve the effector function of immune cells.

Provided herein are chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

The present disclosure provides methods for treating cancer and/or delaying or decreasing cytokine release syndrome in a patient in need thereof comprising administering an effective amount of dexamethasone and an effective amount of tumor-specific T cell engaging multi-specific antibodies. Kits for use in practicing the methods are also provided.