The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Disclosed herein are methods for treatment of a mesothelin (MSLN)-expressing cancer in a human subject comprising administration of, e.g., a plurality of anti-MSLN T cell receptor fusion protein (TFP)-expressing T cells. A ratio of CD4+ to CD8+ T cells in a sample from the human subject may have been determined before the administration of the plurality of anti-MSLN TFP-expressing T cells. The plurality of anti-MSLN TFP-expressing T cells may comprise a pre-determined ratio of CD4+ to CD8+ T cells.

Provided herein are BCMA CARs and CAR-T cells, gamma secretase inhibitors, and the combination thereof. Also provided are the combination of BCMA CAR-T cells and gamma secretase inhibitors for use in treating cancer. In some embodiments, particular dosing regimens, redosing regimens, and combination regimens with lymphodepletion are provided, for the treatment and clinical management of multiple myeloma in subjects in need thereof.

A bone biospecific agent comprises a contrast material core, which is visible using Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The contrast material core is surrounded by a polymeric shell, which is functionalised with a bone-targeting peptide. In use, the peptide targets the biospecific agent to bone. The bone biospecific agent can be used in diagnostic imaging techniques, such as MRI and CT, and in imaging bone remodelling activities, detecting and treating pathological bone conditions and/or bone repair processes. The invention extends to the diagnosis and/or treatment of bone disease and bone pathologies using the biospecific agents.

Provided are methods of treating a KRAS mutant cancer in an individual. In certain embodiments, the methods include administering to an individual identified as having a KRAS mutant cancer a therapeutically effective amount of an agent that inhibits cardiotrophin-like cytokine factor 1 (CLCF1)-ciliary neurotrophic factor receptor (CNTFR) signaling. According to some embodiments, the KRAS mutant cancer is a KRAS mutant lung cancer, such as a KRAS mutant non-small cell lung cancer (NSCLC), e.g., a KRAS mutant lung adenocarcinoma (LUAD). Also provided are kits that find use, e.g., in practicing the methods of the present disclosure.

The present invention relates to compositions and methods for the regulated and controlled expression of proteins. Methods for inducing anti-cancer immune responses in a subject are also provided.

TNFR2-expressing neuroblastoma cells activate monocytes via contact-dependent mTNFα signaling, leading to production of sTNFα and IL-6 by monocytes that in turn bind to TNFR1 and IL-6R on neuroblastoma cells and stimulate tumor growth via activation of NF-κB and Sta3 signaling pathways. Growing tumor recruit additional monocytes resulting in a self-promoting inflammation that fuel tumor growth. TNF inhibitors can terminate this feed-forward signal amplification loop and inhibit tumor growth. Embodiments of the disclosure include a method of using TNF inhibitors for the treatment of neuroblastoma in a subject in need thereof. Also disclosed herein is a method of a method of using TNF inhibitors for reducing tumor-promoting inflammation in an individual with cancer.

This document relates to methods and materials for treating a mammal having an autoimmune disease. For example, materials and methods for producing a T cell comprising a FOXP3 polypeptide and one or more transcription factors are provided herein. Methods and materials for treating a mammal having an autoimmune disease comprising administering to a mammal having an autoimmune disease an effective amount of a T cell are also provided herein.

The present invention relates to medical combination products comprising (i) at least one antibody construct comprising at least one domain which binds to a target antigen expressed on the surface of a cell and at least one other domain which binds to CD3 as well as (ii) at least one molecule that is inhibitor/antagonist of TNF/TNFR reducing TNF/TNFR signaling and/or an inhibitor/antagonist of IL6/IL6R that reduces IL6/IL6R signaling, wherein a first dose of said inhibitor/antagonist is administered before administration of a first dose of said antibody construct. Furthermore, the invention provides therapeutic and preventive methods and medical uses of said combination products, as well as a kit comprising said at least one antibody construct and at least one antagonist/inhibitor of TNF or IL6 or its cognate receptor, wherein the interaction of said antagonist/inhibitor of TNF or an inhibitor/antagonist of IL6 with its cognate receptor reduces, mitigates, prevents, or treats cytokine release syndrome.

The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.