Embodiments relate to a modified cell comprising an antigen binding molecule, and the expression and/or function of one or more genes in the modified cell has been enhanced or reduced or eliminated. The one or more genes include CXCR3, SLC1A3, YAP, TIGIT, S1P1, and IL-35. In embodiments, the cell is a T cell, a dendritic cell, a NK cell, or a macrophage cell. In embodiments, the antigen binding molecule comprises a chimeric antigen receptor (CAR) and/or the second antigen binding molecule is a T Cell Receptor (TCR).

The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

Compositions, e.g., compositions comprising protein therapeutics, and methods of using such compositions for treating cancer are described.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to 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.

The present disclosure provides Multimeric Antigen-Presenting Polypeptides (MAPPs) for the presentation of epitopes in the context of a class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. MAPPs are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers, autoimmune diseases and/or allergies.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to 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.

In some embodiments, marrow-infiltrating lymphocytes (“MILs”) comprising a chimeric antigen receptor (“CAR”) are provided. In some aspects, the embodiments relate to a MIL obtained from bone marrow comprising a chimeric antigen receptor. In some aspects, the embodiments relate to a method for treating a condition in a subject, comprising administering to the subject a MIL comprising a CAR.

The present application relates to a tumor specific neoantigenic peptide, wherein said peptide is encoded by a part of an ORF sequence from a transcript associated with a SF3B1 or a SF3B1-like mutation, comprises at least 8 amino acids and binds at least one MHC molecule with an affinity of less than 500 nM; and is not expressed in normal healthy cells. The present application further relates to vaccine or immunogenic composition, antibodies, T cell receptors, polynucleotides, vectors and immune cells derived thereof as well as their use in therapy of cancer.

The antigen-presenting cell loaded with the cancer-specific tumor antigen epitope provided in the present invention, that is, a dendritic cell enables rapid and effective induction of differentiation and proliferation of cancer antigen-specific T cells, preferably memory T cells, and the memory T cells thus activated can treat a cancerous or neoplastic condition or prevent recurrence, progression, or metastasis of cancer while avoiding the defense mechanism of cancer cells.

The present invention relates to an immune cell that are engineered to overexpress cell signaling pathway modulator(s) and a use thereof. As a specific example, an immune cell expressing a fusion protein comprising a chimeric antigen receptor and a cell signaling pathway modulator(s) performs an immune response by selecting a target cancer cell by a chimeric antigen receptor expressed on a cell membrane. In this case, the cell signaling pathway modulator is overexpressed in the cytoplasm, thereby being capable of regulating the activity of an immune cell. Therefore, the fusion protein comprising a chimeric antigen receptor and cell signaling pathway modulator(s), and the immune cell engineered to overexpress the cell signaling pathway modulator(s) of the present invention can be usefully used in the treatment of cancer.