The objective of the invention is to provide cross-species anti-latent TGF-beta 1 antibodies which inhibit a protease mediated activation of latent TGF-beta 1 without inhibiting integrin mediated activation of latent TGF-beta 1. To obtain the anti-latent TGF-beta 1 antibodies of the invention, anti-latent-latent TGF-beta 1 antibodies which inhibit a protease mediated activation of latent TGF-beta 1 without inhibiting integrin mediated activation of latent TGF-beta 1 were screened, and then humanized, and further optimized. The invention also provides combination therapies comprising an anti-latent TGF-beta 1 antibody and one or more immune checkpoint inhibitors, preferably a PD-1 axis binding antagonists.

Affinity binding entities having TCRL binding domain and methods of their use are provided. More specifically these compositions bind HLA-A2/WT1+, HLA-A2/MAGE-A4, HLA-A2/MAGE-A9, HLA-A2/PAP or HLA-A2/TyrD+ cells and as such can be used in diagnostics and therapy.

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Aspects of the invention include compositions and methods for treatment of solid tumors with engineered or non-engineered γδ-T cells. In some embodiments, the γδ-T cells comprise a chimeric antigen receptor (CAR) construct. The CAR construct can contain an anti-TryD binding domain, a CD8α hinge and transmembrane domain, a costimulatory domain, a 003ζ signalling domain, a combination thereof, or all thereof. The CAR construct can contain an anti-GPC3 binding domain, a CD8α hinge and transmembrane domain, a costimulatmy domain, a CD3ζ signalling domain, a combination thereof, or all thereof. The CAR construct can contain a domain encoding for a secreted common gamma chain cytokine such as a sIL 15 domain.

Engineered antibodies useful for site-specific conjugation by a transglutaminase are described. Also described are methods of site-specific conjugation of the antibodies, the site-specifically conjugated antibodies, and pharmaceutical compositions and uses related to the site-specifically conjugated antibodies.

An antibody or antigen binding fragment thereof that binds to an IL-36, wherein the antibody or antigen binding fragment thereof binds to both IL-36α and IL-36γ, and wherein the antibody is an antagonist of both IL-36α and IL-36γ.

Provided herein are methods of modulating immune response, including methods of treating a cancer or an infection using a combination of kinase modulators and immunotherapy that promotes immune response. Also provided herein are methods of treating an autoimmune disease or graft-versus-host disease, and methods of reducing the risk of solid organ transplant rejection using a combination of kinase modulators and immunosuppressive therapy.

The specification describes the sequences for antibodies that recognize the HLA-A2-restricted peptide PR-1 in the context of HLA presentation on the surface of cancer cells. Use of these antibodies in the diagnosis and treatment of cancer and immune-related diseases are also provided.

Provided herein are antibodies that selectively bind to complex comprising a non-classical HLA-I (e.g. HLA-E) and a neoantigen having variable heavy chain domains (VH), variable light chain domains (VL), and complementarity determining regions (CDRs) as disclosed herein, as well as methods and uses thereof.

The present invention is directed to a novel naturally occurring human cytokine that is comprised of a heterodimer of interleukin-17 and interleukin-17F designated herein as interleukin 17A/F (IL-17A/F). Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, specific antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.