Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.

A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.

The present invention relates to the field of manufacturing of Natural Killer (NK) Cells genetically modified with viral vectors carrying a polynucleotide coding for a Chimeric Antigen Receptors (CARs). The present invention further relates to CAR-NK cells obtained with the method and use of the CAR-NK cells in medicine, in particular for use in a method of treating cancer.

Compositions including an antibody single-chain variable fragment (scFv) conjugate that specifically binds to ROR1 tumor-associated antigen are provided. The anti-ROR1 scFv antibody and conjugates may include a biologically-active molecule. Such conjugates may comprise a chimeric receptor to direct T cells to respond to ROR1 cancer cells, Methods to use the scFV conjugates to target cells expressing ROR1 for therapeutic and diagnostic purposes are also provided.

The disclosure provides modified NK cells and pharmaceutical compositions comrpsing the same. The disclosure also provides methods of treating cancer using the same.

The present disclosure relates to methods of treating a solid tumor with an IL-7 protein in combination with a population of modified immune cells, e.g, CAR-bearing immune cells (e.g., CAR-T cells or iNKT-CAR cells) and/or transgenic TCR-bearing immune cells.

The present invention generally relates to T-cells, such as CD8+ T-cells, CD4+ T-cells, CD3+ T-cells, γδ T-cells or natural killer (NK) T-cells, transfected/transduced with a fusion protein which is recruited by the use of trivalent, bispecific antibody molecule which specifically binds to/interacts with the extracellular domain of the fusion protein. More precisely, the present invention relates to a kit comprising the nucleic acid molecules, vectors and/or the fusion proteins of the present invention and the trivalent, bispecific antibody molecules of the present invention. Further aspects of the inventions are expression vectors comprising nucleic acid molecules encoding the fusion proteins as well as the trivalent, bispecific antibody molecules. Further, a process for the production of the trivalent, bispecific antibody molecules of the invention and a medicament/pharmaceutical composition comprising said trivalent, bispecific antibody molecules are described. The invention also provides the use of said trivalent, bispecific antibody molecules in a method for the treatment of particular diseases as well as a pharmaceutical compositions/medicament comprising said trivalent, bispecific antibody molecules, wherein said trivalent, bispecific antibody molecule(s) is (are) to be administered in combination with transduced T-cells comprising the fusion protein of the invention. The invention also provides a method for the treatment of particular diseases.

The invention provides compositions and methods for suppressing autoimmune components of neurodegenerative diseases and thereby providing therapeutic effects to patients suffering from such diseases, Compositions and methods include immunosuppressive moieties such as regulatory T cells (Tregs) and proteins expressed by Tregs coupled to a chimeric antigen receptor or protein that specifically binds one or more glial cell markers. Therapeutically effective doses of said compounds for treating neurodegenerative diseases including progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's, Huntington's disease, amyotrophic lateral sclerosis (ALS), chronic traumatic encephalopathy (CTE), multiple sclerosis, and prion diseases are disclosed.

The present invention relates to compositions and methods for using a minibody. Minibodies described herein comprise a secretion signal, a variable heavy chain fragment, a variable light chain fragment, a constant chain fragment, and a hinge domain between the variable light chain fragment and the constant chain fragment. One aspect includes a nucleic acid encoding a minibody. Other aspects include compositions comprising a minibody and a modified T cell comprising a nucleic acid encoding a minibody. Also included are methods and pharmaceutical compositions comprising the modified T cells for adoptive therapy and treating a condition, such as cancer.

The present invention relates to an immune cell that are engineered to overexpress cell signaling pathway modulator(s) and a use thereof. As a specific example, an immune cell expressing a fusion protein comprising a chimeric antigen receptor and a cell signaling pathway modulator(s) performs an immune response by selecting a target cancer cell by a chimeric antigen receptor expressed on a cell membrane. In this case, the cell signaling pathway modulator is overexpressed in the cytoplasm, thereby being capable of regulating the activity of an immune cell. Therefore, the fusion protein comprising a chimeric antigen receptor and cell signaling pathway modulator(s), and the immune cell engineered to overexpress the cell signaling pathway modulator(s) of the present invention can be usefully used in the treatment of cancer.