Provided herein are compositions and methods for the treatment of cancers using modified TILs, wherein the modified TILs include one or more immunomodulatory agents (e.g., cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and/or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

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 eliciting an anti-cancer immune response by administering tumor-associated antigens, cells containing tumor-associated antigens, and/or nucleic acids encoding tumor-associated antigens. inducing immunogenic cell death in the cells expressing or containing the tumor-associated antigens. and optionally generating hyperactivated dendritic cells. Expression of tumor-associated antigens in a separate anatomical site generates a tumor avatar, which mimics the antigenic, but not immunosuppressive, environment of the tumor, with the generation of hyperactivated dendritic cells enhancing antigen presentation to elicit a robust anti-tumor T cell and antibody response. Also provided are compositions and kits containing nucleic acids and other components for use in the methods provided herein.

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

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

The present invention relates to chimeric transmembrane immunoreceptors, named zetakines, comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human maligancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targetting domain of the IL-13R2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

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.

Provided are polynucleotides encoding inactivated cell surface receptors. Also provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

The present disclosure provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.