Methods for neutralizing and/or removing human GM-CSF in a subject in need thereof, comprising administering to the subject CAR-T cells having a GM-CSF gene knockout (GM-CSF.sup.k/o CAR-T cells) are provided. Also provided are methods for GM-CSF gene inactivation or GM-CSF knockout (KO) in a cell comprising targeted genome editing or GM-CSF gene silencing. Methods for preventing/treating immunotherapy-related toxicity, comprising administering to the subject CAR-T cells having a GM-CSF gene inactivation or GM-CSF knockout (GM-CSF.sup.k/o CAR-T cells), wherein the GM-CSF gene is inactivated or knocked out and/or or a recombinant GM-CSF antagonist are provided. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having immunotherapy-related toxicity comprising administering to the subject a recombinant hGM-CSF antagonist are provided. Also provided are methods for treating or preventing immunotherapy-related toxicity in a subject, 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). Methods for preventing or reducing blood-brain barrier disruption in a subject treated with immunotherapy, the method comprising administering CAR-T cells having a GM-CSF gene knockout (GM-CSF.sup.k/o CAR-T cells) to the subject, also are provided.

The present invention relates to novel tumor-associated antigens, which elicit independently from a presentation via MHC a CD8-positive T-cell response. GM-CSF-Receptor alpha chain (CSF2RA) and Tyrosinase-related protein 2 (TRP-2) were found to be targets of CD8-positive T-cell clones which could detect the proteins on the surface of HLA I negative melanoma cells. Thus, the invention provides proteins, protein fragments and polypeptides of the novel antigens for use in medicine, for example for the treatment, diagnosis and prevention of a tumor disease. Furthermore provided are nucleic acids expressing the antigens of the invention, binding agents specific for the antigens of the invention, such as T-cell receptor chains and isolated T cells which are reactive against the antigens of the invention or which express the T-cell receptors of the invention. The invention further pertains to pharmaceutical compositions, especially vaccine compositions, comprising the antigens, nucleic acids, binding agents or T cells in accordance with the invention, and methods for the generation of T cells, which are specifically reactive to the antigens of the invention in an MHC-independent manner.

Provided herein are immunomodulatory proteins comprising variant PD-L2 and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CARs include a tumor antigen-specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, a GPC2-specific or a mesothelin-specific monoclonal antibody, fused to a CD8 hinge region, a CD8 transmembrane region, a 4-1BB co-stimulatory domain and a CD3 signaling domain. Isolated host cells, such as isolated T cells that co-express the disclosed CARs and huEGFRt are also described. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

The present application provides an anti-CD5 antibody. The present application further provides a chimeric antigen receptor (CAR) that specifically binds to a CD5 protein, which comprises a CD5 binding domain, a transmembrane domain, a co-stimulatory domain and an intracellular signaling domain. Further provided are engineered immune effector cells (such as T-cells) comprising the chimeric antigen receptor. The present application further provides use of the CAR and the engineered immune effector cells in the treatment of diseases or conditions associated with the expression of CD5.

The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen bindingtransmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3 intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The present invention discloses cell lines and recombinant growth factor receptors useful in adoptive cell therapy (ACT), wherein the recombinant growth factor receptor can act as a molecular switch enabling cells expressing the rGFR protein to be expanded in-vitro or in- vivo. Thus the invention provides a T or NK cell, comprising a recombinant growth factor receptor (rGFR) comprising: (i) an extracellular (EC) domain; (ii) a thrombopoietin receptor transmembrane (TM) domain; and (iii) a growth factor receptor intracellular (IC) domain.

A novel synthetic biology-based ADCC technology is provided that enhances or enables ADCC response. The novel ADCC technology can be used to prevent or treat cancers, infectious, inflammatory or autoimmune diseases, and other diseases where elimination of diseased cells is desirable.

The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen binding-transmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3 intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The present invention relates, in part, to, chimeric proteins which include the extracellular domain of colony stimulating factor 1 receptor (CSF1R) and their use in the treatment of diseases, such as immunotherapies for cancer and/or an inflammatory disease.