Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

The invention provides methods of preventing or treating ocular diseases and conditions by adoptive transfer of plasmacytoid dendritic cells and related compositions.

The invention provides chimeric antigen receptors (CARs) that specifically bind to the T-cell immunoglobulin and mucin domain 1 (TIM-1) protein. The invention further relates to modified immune cells, e.g., T or NK cells, comprising such CARs, CAR-encoding nucleic acids, CAR-encoding vectors, and methods of making such compositions. The invention further relates to methods for therapeutic use of these CARs and modified immune cells for the treatment of a condition, disorder, or disease associated with cells expressing TIM-1 (e.g., cancer).

Implantable scaffolds that treat solid tumors and escape variants and that provide effective vaccinations against cancer recurrence are described. The scaffolds include genetically-reprogrammed lymphocytes and a lymphocyte activating moiety.

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 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 present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with a V600 mutation with TILs as described herein in combination with BRAF inhibitors and/or MEK inhibitors.