The present disclosure provides therapeutic agents and uses thereof for drugs for treatment of tumors and/or cancers. The active ingredients of the therapeutic agents comprise an oncolytic virus that selectively replicate in tumor cells and comprise NK cells.

Provided herein are tumor-antigen VCX/Y specific peptides and engineered VCX/Y specific T cell receptors. Also provided herein are methods of generating VCX/Y-specific immune cells and their use for the treatment of cancer. In addition, the VCX/Y-specific peptides may be used as a vaccine.

The invention provides compositions and methods for administering a therapeutic agent to a patient, such as pharmaceutical compositions containing a blood product and a therapeutic agent selected from an anthracycline anti-cancer agent (e.g., doxorubicin), a topoisomerase inhibitor, an oxazaphosphinanyl anti-cancer agent, a nitro-aryl anti-cancer agent, a thiol-reactive functional-group agent, a nitric oxide modulator, a platinum-based antineoplastic compound, acrylamide, acrylonitrile, bis(4-fluorobenzyl)trisulfide, a cardiac glycoside, an anti-mitotic agent (e.g., paclitaxel), a nucleoside analog, an EGFR inhibitor, or an anti-microbial agent.

Provided is an GARP protein antibody, and a cell comprising or expressing the GA RP protein antibody. The GARP protein antibody binds to human GARP/human TGF-?1 complex with a K.sub.D value of about 1.0E-12 or less. Also provided are a pharmaceutical combination comprising the GARP protein antibody and an immune checkpoint inhibitor and use thereof.

Provided herein are recombinant nucleic acids encoding a T cell receptor (TCR) fusion protein (TFP) and an interleukin-15 (IL-15) polypeptide and/or an interleukin-15 receptor alpha (IL-15R?) polypeptide, modified T cells expressing the encoded molecules, and methods of use thereof for the treatment of diseases, including cancer.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

Provided are agents comprising a phosphatidylcholine as an active ingredient to serve as a vein-formation promoting agent capable of promoting vein-like morphological change of tumor vessels, a vessel-diameter enlarging agent capable of enlarging the diameter of tumor vessels, a blood vessel-connection promoting agent capable of promoting connection of tumor vessels to each other without mediation of a lysophospholipid receptor, a leukocyte-infiltration promoting agent capable of promoting infiltration of leukocytes throughout a tumor region without mediation of a lysophospholipid receptor, and an antitumor immunostimulatory agent capable of promoting infiltration of leukocytes throughout a tumor region without mediation of a lysophospholipid receptor.

Disclosed are T-cell receptors (TCRs) binding to tumor-associated antigens (TAAs) for targeting cancer cells, T-cells expressing same, methods for producing same, and methods for treating cancers using same. Disclosed are TCRs and their variants that bind to HLA class I or II molecules with a peptide, such as MAG-003 have the amino acid sequence of KVLEHVVRV (SEQ ID NO:1). The description further relates to peptides, proteins, nucleic acids, cells for use in immunotherapeutic methods, the immunotherapy of cancer, and tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Described herein are compositions and methods for treating a disease, particularly a cancer, with an immune checkpoint modulatory agent and a strain of an Arbovirus or a strain of an Alphavirus. Also provided herein are also methods for combination therapy comprising administration of an immune checkpoint modulatory agent, tumor antigen primed dendritic cells and an Alphavirus or an Arbovirus.

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.