The present disclosure relates to IL12 receptor agonists with improved therapeutic profiles.

The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Provided herein are target HLA-PEPTIDE antigens, e.g., HLA-PEPTIDE neoantigens and shared tumor HLA-PEPTIDE antigens, and antigen binding proteins (ABPs) that bind the target HLA-PEPTIDE antigens. Also disclosed are methods for identifying target HLA-PEPTIDE antigens as well as identifying one or more antigen binding proteins that bind a given HLA-PEPTIDE target antigen.

A TCR-like antibody or an antigen-binding fragment thereof, the antibody binding to and having specific and improved affinity to an MHC-I molecule, particularly a CMV pp65 peptide complex (CMVP495-503/HLA-A*02:01) presented by HLA-A*02 are disclosed. A nucleic acid for coding the TCR-like antibody or the antigen-binding fragment thereof; an expression vector containing the nucleic acid; a cell transformed to the expression vector; a method for producing same; a composition containing a T cell for expressing the antibody or the antigen-binding fragment thereof as a chimeric antigen receptor; uses of the composition in preventing or treating cancer or an infectious disease; uses of the composition in diagnosis; methods for preventing and/or treating cancer or infectious diseases; and methods for diagnosing are disclosed.

A multispecific nanobodies chimeric antigen receptor and T-cell engager includes an HLA-G nanobody chimeric antigen receptor and a bispecific T-cell engager. The HLA-G nanobody chimeric antigen receptor includes an HLA-G nanobodies unit, a transmembrane domain, and a CD3z signaling domain. The bispecific T-cell engager includes a PD-L1 nanobodies unit and a CD3e nanobody.

The invention provides anti-MIC antibodies and methods of using the same.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule CI for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.