The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

An anti-EGFRviii antibody, a polypeptide, a cell expressing the polypeptide, a pharmaceutical composition containing the cell, a method for producing the cell, and a polynucleotide or a vector including a nucleotide sequence encoding the polypeptide.

The present disclosure relates to cells capable of co-expressing T cell receptors (TCR) together with membrane-bound IL-15 polypeptides and/or CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified IL-15, IL-15R, IL-15/IL-15R fusion polypeptide, and IL-15R/IL-15 fusion polypeptide sequences, vectors, and associated methods of making and using the same. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods of making and using the same.

Provided herein are allogenic tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL 15). The allogeneic mbIL 15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in allogeneic adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The allogeneic TIL can be further engineered such that the mbIL 15 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 methods of screening for efficacy of allogeneic TILs using an allogeneic patient derived xenograft.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Disclosed herein are methods of producing a hypoimmune cell and methods of mediating localized immune tolerance.

The disclosure is directed, in part, to novel drug-responsive T cell factors providing temporal and/or spatial control over T cell (e.g., CAR T cell) activation and/or proliferation, T cells comprising the T cell factors, nucleic acid encoding the T cell factors, and methods for using and producing the same.

This disclosure relates to leukocyte compositions that comprise immune cells that are modified for enhanced in vivo anti-tumor activity. The leukocyte compositions are enriched for CD4+ Th1 cells or other differentiated states and optionally depleted of CD8+ T cells.

The present disclosure provides compositions of immune cells presenting a target molecule or a fragment thereof and provides compositions and methods of producing immune cell therapies with targeted activity against cancer. Methods for conditioning a subject receiving the immune cell therapy of the disclosure are additionally disclosed. The immune cell therapies of the present disclosure can be administered to a subject in need thereof for diseases such as cancer.