The present invention relates to compositions and methods for cancer therapy, including but not limited to, therapies that utilize cancer biomarkers. In particular, the present invention relates to compositions and methods for the prediction of a subject's response to cancer therapies.

Experimental and clinical evidence suggests tumor-associated macrophages (TAM) play important roles in cancer progression. Here, the inventors show that the omentum is a critical pre-metastatic niche for development of invasive disease in this model and defined a unique subset of CD163+ Tim4+ tissue-resident macrophages in omentum of embryonic origin and maintained independently of bone marrow-derived monocytes. Transcriptomic analysis showed that resident CD163+ Tim4+ omental macrophages were phenotypically distinct and maintained their resident identity during tumor growth. Selective depletion of CD163+ Tim4+ macrophages in omentum using genetic and therapeutic tools prevented tumor progression and metastatic spread of disease. The molecular pathways of cross-talk between tissue-resident macrophages and disseminated cancer cells may represent new targets to prevent metastasis and disease recurrence. Thus the present invention relates to a method of treating ovarian cancer, breast cancer and pancreatic cancer in a subject in need thereof comprising administering to the subject a therapeutically effective of an agent capable of depleting the population of CD163+ Tim4+ tumor associated macrophages.

Methods of treating acute liver disease acute liver diseases are provided. Accordingly, there is provided a method of treating acute liver disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an agent capable of binding a component of a TLR-MYC signaling pathway selected from the group consisting of MYC, MYD88, TRIF and p38 and inhibiting expression and/or activity of the component.

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 engineered non-catalytic, non-toxic tetanus toxin variants and methods of using such engineered tetanus toxin variants as low dose, protective vaccines that are non-toxic and more potent than their respective chemically inactivated toxoids. In addition, provided herein are conjugate vaccine carriers comprising engineered tetanus toxin variants and methods of using such conjugate vaccines to elicit T-cell dependent immune memory responses which can target a broad spectrum of microbial pathogens as a single vaccine.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Provided herein are antibodies comprising acceptor glutamine sequences at site-specific positions, compositions comprising the antibodies, conjugates of the antibodies, methods of their production, and methods of their use. The antibodies are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

Bivalent epidermal growth factor (EGF) fusion toxin including two EGF domains are provided. The described fusion toxin demonstrates increased binding and cytotoxicity when compared to a fusion toxin having a single EGF binding domain (monovalent). Methods for treating epidermal growth factor receptor (EGFR)-positive cancers and related materials are also provided.

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that arc engineered to express a CTX-CAR described herein.

The present invention generally relates to T cell activating bispecific antigen binding molecules, PD-1 axis binding antagonists, and in particular to combination therapies employing such T cell activating bispecific antigen binding molecules and PD-1 axis binding antagonists, and their use of these combination therapies for the treatment of cancer.