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.

It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.

The invention relates to the combined use of certain bispecific, VEGF and Ang2 binding molecules with PD1 antagonists for the treatment of cancer. It further relates to pharmaceutical compositions and kits comprising such binding molecules and antagonists.

The present invention provides antibodies that bind to the class Ill variant of EGFR (EGFRvIII) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human EGFRvIII with high affinity. The antibodies of the invention may be fully human antibodies. The invention includes anti-EGFRvIII antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers.

The invention provides methods or compositions for enhancing the potency of a targeted cancer immunotherapy in a subject by using a superantigen in combination with a PD-1 inhibitor.

Antibodies that specifically bind to a Sonic Hedgehog (Shh) polypeptide, or an antigen binding fragment thereof, are provided. Also provided are methods of treating an individual for cancer using the Shh polypeptide antibodies. Methods of analyzing a tissue sample for cell-surface expression of a full-length Shh polypeptide are also provided.

Antibody drug conjugates (ADC's) that bind to 158P1D7 protein and variants thereof are described herein. 158P1D7 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in glioblastoma, lung cancer, bladder cancer, and breast cancer. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a VEGFR inhibitor, and the use of the combination therapies for the treatment of cancer, and in particular for treating cancers that express PD-L1.

Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1, block binding of PD-L1 to PD-1 and promote internalization and degradation of PD-L1 are provided. Antibodies that recognize specific epitopes on glycosylated PD-L1 protein and that exhibit the dual functions of both blocking the binding of PD-L1 to PD-1 and also facilitating the internalization of PD-L1 on cells are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for using such antibodies for the treatment of cancer, particularly PD-L1 positive cancer, are also provided.

Provided herein are antibodies, or antigen binding portions thereof, that bind to OX40. Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.