Provided herein are T.sub.RM cells, compositions thereof and methods of use thereof. The T.sub.RM cells inhibit profibrotic gene expression, suppress profibrotic inflammatory conditions, and inhibit and remediate fibrotic pathogenesis. The T.sub.RM cells can localize to specific tissues, enabling tissue and organ-targeted treatment. The methods of use include methods of treating and/or preventing fibrosis, including pulmonary fibrosis.

The present invention is directed to 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 binds to human PLAP (placental alkaline phosphatase), (ii) a transmembrane domain, (iii) a co-stimulatory domain of CD28, OX-40, GITR, or 4-1BB, and (iv) CD3 an activating domain. The present invention is also directed to T cells, natural killer (NK) cells, or macrophages, modified to express the CAR of the present invention. The present invention is further directed to a method for treating PLAP-positive cancer cells by administering PLAP-CAR-T cells, PLAP-CAR-NK cells, or PLAP-CAR-macrophages to the patients.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

The present invention relates to the treatment of autoimmune and allergic diseases by mucosal delivery by micro-organism, in particular Lactococcus lactic, of secreted immunodominant antigens.

Methods for treating cancer are disclosed which comprise administering to a subject T cells which have been pretreated ex vivo or in vitro with a fatty acid catabolism promoter to condition the T cell to use fatty acids rather than glucose for energy production. Still other methods comprise co-administering to a subject having a cancer characterized by a solid tumor (a) an immunotherapeutic composition targeting an antigen or ligand on the tumor cell; and (b) a compound or reagent that promotes the use of fatty acid catabolism by tumor antigen-specific T cells in the tumor microenvironment and/or T cells pretreated ex vivo with the fatty acid catabolism promoter to condition the T cell to use fatty acids rather than glucose for energy production for adoptive cell transfer. Both methods may also employ co-administration of a checkpoint inhibitor.

Provided herein are innate immune cells for use in therapeutic methods. Also described herein are pharmaceutical compositions comprising innate immune cells for use in the treatment of a variety of diseases including, but not limited to pathogenic infections, pulmonary diseases, inflammatory diseases, autoimmune diseases, and immunodeficiency.

A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.

In some aspects the present invention provides methods for the treatment of B-cell lymphomas. Some such methods involve administration of HVEM ectodomain polypeptides, anti-HVEM antibodies, or anti-BTLA antibodies to subjects in need thereof. Some such methods involve use of CAR T cells, such as CD19-specific CAR T cells. The present invention also provides compositions useful in such methods. These and other embodiments of the present invention and described further herein.

The present disclosure provides a composition comprising isolated T cells, wherein the T cells have specificity against a range of clinical fungal pathogens.

As described herein, the activity of Treg cells can be mediated by cathepsin inhibition, e.g., in tumor environments, cathepsin inhibition results in increased Treg anti-tumor activity, while in non-tumor environments, cathepsin inhibition results in increased immunosuppressive activity. Accordingly, provided herein are methods of modulating Treg activity and methods of treating diseases (e.g., cancer or autoimmune diseases) by inhibiting cathepsins in Treg cells.