The invention provides compositions, methods, and vaccines that may stimulate the immune system and that may be used for treating malignancies associated with overexpression of the HER3 protein. Such compositions include epitopes of the HER3 protein.

This document relates to methods and materials related to isolated polypeptides, polypeptide preparations, and methods for using one or more isolated polypeptides to activate T cells. For example, polypeptides that can be used to activate T cells to generate antigen-specific T cells are provided. In some cases, T cells activated as described herein can be administered to a mammal having cancer (e.g., MM) or a precancerous condition (e.g., MGUS) to treat the mammal (e.g., to induce an immune response against the cancer or the precancerous condition).

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

The present disclosure provides compositions comprising anti-LMP2 TCR-T cell populations for the treatment of EBV-associated cancers and methods of making and using same.

Embodiments of the disclosure include immune cells expressing HER2-specific chimeric antigen receptors (CAR) and treatment of cancer therewith. In specific embodiments, sarcoma or glioblastoma are treated. In specific embodiments, such as for glioblastoma, for example, T-cells expressing a HER2-specific CAR are pp65CMV-specific T cells.

Provided herein are antibodies that specifically bind to GPRC5D. Also described are related polynucleotides capable of encoding the provided GPRC5D-specific antibodies or antigen-binding fragments, cells expressing the provided antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled antibodies or antigen-binding fragments. In addition, methods of using the provided antibodies are described. For example, the provided antibodies may be used to diagnose, treat, or monitor GPRC5D-expressing cancer progression, regression, or stability; to determine whether or not a patient should be treated for cancer; or to determine whether or not a subject is afflicted with GPRC5D-expressing cancer and thus may be amenable to treatment with a GPRC5D-specific anti-cancer therapeutic, such as the multispecific antibodies against GPRC5D and CD3 described herein.

Provided herein are methods and compositions for treating chordoma by preferentially targeting cancer stem cells than non-cancer stem cells in chordoma to effectively treat chordoma. In some embodiments, the chordoma tumors cells (preferentially the cancer stem cells in chordoma) are targeted by modified NK-92 cells (i.e., haNK cells) that express CARs that comprise means for binding to the PD-L1 and another tumor-specific antigen (e.g., EGFR). In some embodiments, the chordoma tumor cells are targeted by using NK cells in combination with a means for binding to means for binding to the PD-L1 and/or a means for binding another tumor antigen (e.g., EGFR). Each of the treatment methods disclosed above may be implemented prior to, and/or concurrent with radio- and/or chemotherapy, and/or may be employed with immune therapy as is discussed in more detail below.

Described herein are antigen binding proteins with specificity to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC). Also described are multispecific antigen binding proteins comprising an antigen binding domain with specificity to CD3, and at least one MAGE-A4 pMHC antigen binding domain. Methods of treating cancer with the same are also described.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. NK cells have effector activity within the TME, under continuous ligand exposure. NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. We created NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3 to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PDL1+ target cells.