Methods for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy, in an absence of an incidence of immunotherapy-related toxicity or in a presence of immunotherapy-related toxicity. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having an incidence of immunotherapy-related toxicity, the methods comprising administering a recombinant GM-CSF antagonist to the subject. Methods for treating or preventing immunotherapy-related toxicity in a subject, the methods comprising administering to the subject chimeric antigen receptor-expressing T-cells (CAR-T cells), the CAR-T cells having a GM-CSF gene knockout (GM-CSF.sup.k/o CAR-T cells), and a recombinant hGM-CSF antagonist.

The present invention provides a chimeric antigen receptor (CAR) fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising V.sub.H and V.sub.L, wherein scFv has an activity against CD47, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. In one embodiment, the scFv is derived from a humanized anti-CD47 antibody. The present invention also provides T cells modified to express the CAR of the present invention.

The present disclosure provides therapeutic agents and uses thereof for drugs for treatment of tumors and/or cancers. The active ingredients of the therapeutic agents comprise an oncolytic virus that selectively replicate in tumor cells and comprise NK cells.

The invention features compositions and methods useful in treating inflammation of the gut, such as inflammation associated with inflammatory bowel disease, by modulating ?? T cells (e.g., V?4+ cells). Particular embodiments include V?4+ cells expressing heterologous protein; polynucleotides containing genes contributing to functional expression of BTNL3, BTNL8, and HNF4A; methods of treating a subject using V?4+ cells or gene therapy; and methods of identifying a subject having imitations associated with inflammation of the gut. Compositions and methods of the invention can be used in the treatment of inflammation and cancer of the gut.

The invention provides inter alia an engineered T cell, wherein said T cell is engineered to express a T cell receptor (TCR) or an antibody-based receptor that binds to a T cell epitope of human ropporin-1A (ROPN1) or human ropporin-1B (ROPN1B); wherein said T cell epitope is selected from the group consisting of SEQ ID NO:4, SEQ ID NO:43, SEQ ID NO:23, SEQ ID NO:56 and SEQ ID NO:24.

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

The invention relates to an immunomodulatory substance(s) and/or a skin-conditioning agent for use in a method for treating and/or preventing an inflammatory disease, immunological disease and/or autoimmunological disease in a subject, wherein the method comprises a step (A) selected from one or more of: generating an accumulation of PBMCs within the skin, generating a vasodilation of the capillaries within the skin, generating an increased blood volume within the skin, generating an increased sO.sub.2 within the skin, generating an increased rHb within the skin, generating an increased temperature on the skin, generating a redness on the skin, administering conditioning energy to the skin, administering a skin-conditioning agent to the skin or administering PBMCs to the skin of the subject; and the method further comprises step (B) administering a first immunomodulatory substance(s) to the skin of the subject and/or step (C) administering a second immunomodulatory substance(s) to the skin of the subject.

Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.

Provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising engineered immune cells that overexpress miR200c and/or EpCAM.

Memory-like cytokine enhanced NK (M-CENK) cells have superior cytotoxicity and can be generated/expanded from a single batch of mononuclear cells to in sufficient quantities to so form a cell-based therapeutic suitable for infusion. Advantageously, the M-CENK cells can be cryopreserved and thawed without compromising viability and cytotoxicity.