Compositions and methods are provided for treating diseases associated with CD100, including certain autoimmune diseases, inflammatory diseases, and cancers. In particular, anti-CD100 monoclonal antibodies have been developed to neutralize CD100.

Methods and compositions for treating autoimmune diseases and conditions using engineered myeloid cells.

Described herein is a therapeutic cell that expresses a fusion protein comprising: (a) a target-binding domain; and (b) a degradation domain, e.g., a degron or E3 ligase-recruiting domain, that is heterologous to the target-binding domain. In the therapeutic cell, binding of the fusion protein to a target protein via the target-binding domain induces degradation of the target protein. The therapeutic cell can be an immunostimulatory cell, an immunoinhibitory cell or a stem cell, for example. Methods of treatment using the cell are also provided.

A population of genetically engineered T cells, comprising a nucleic acid encoding an anti-CD83 CAR, a disrupted Reg1 gene, and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD83 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-β, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

Provided a chimeric anti-drug antibody receptor (CADAR) specific for anti-drug-antibody-based B cell receptor (BCR), the anti-drug antibody is induced by a therapeutic anti-TNF-alpha monoclonal antibody. Also provided compositions comprising the CADAR, polynucleotides encoding the CADAR, vectors comprising a polynucleotide encoding the CADAR, engineered cells comprising the CADAR, and method using the same.

Provided herein, inter alia, are compositions and methods for reprogramming immune cells for treating or preventing immune disorders. The methods include contacting immune cells with antigens, and administering the resultant immune cells to a subject who has an immune disorder.

The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an autoantibody, vectors comprising the same, compositions comprising CAAR vectors packaged in viral particles, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified T cell expressing a CAAR (CAART) wherein the expressed CAAR comprises a desmoglein extracellular domain.

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an autoantibody, vectors comprising the same, compositions comprising CAAR vectors packaged in viral particles, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified T cell expressing a CAAR (CAART) wherein the expressed CAAR comprises a desmoglein extracellular domain.

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an autoantibody, vectors comprising the same, compositions comprising CAAR vectors packaged in viral particles, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified T cell expressing a CAAR (CAART) wherein the expressed CAAR comprises a desmoglein extracellular domain.