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 relates to recombinant human adenoviruses engineered to express a structural protein of a coronavirus. The recombinant adenoviruses are suitable for active immunization against a coronavirus in a human subject. Additionally, immune globulin obtained from immunized human subjects is suitable for passive immunization of a coronavirus-infected human subject.

The present disclosure relates to methods for enhancing the efficiency of therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells, even when provided to a subject in sub-therapeutic amounts, are extremely effective in the treatment of cancer diseases, even those cancer diseases that are known to be difficult to treat with antigen receptor-engineered immune effector cells, such as solid tumors or cancers, if additionally target antigen for the antigen receptor is provided to the subject. Immune effector cells may be engineered ex vivo or in vitro and subsequently the immune effector cells may be administered to a subject in need of treatment, or immune effector cells may be engineered in vivo in a subject in need of treatment.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

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Provided are methods of treating cancer or increasing, enhancing, or stimulating an immune response with non-competitive, agonist anti-OX40 antibodies and antigen-binding fragments thereof that bind to human OX40 (ACT35, CD134, or TNFRSF4), in combination with an anti-TIGIT antibody or fragment thereof.

The disclosure relates to methods and materials for treating cancer. For example, recombinant vaccinia viruses having the ability to direct the expression of membrane-bound IL-12 polypeptides on the surface of infected cells and methods for using such recombinant vaccinia viruses to treat cancer are provided. Specifically, the disclosure provides a recombinant vaccinia virus comprising a vaccinia virus genome comprising a nucleic acid encoding an IL-12p35 polypeptide sequence and an IL-12p40 polypeptide sequence, wherein one of the polypeptide sequences comprises a membrane anchoring polypeptide sequence.

PD1-CD70 fusion proteins are provided. Accordingly, there is provided a PD1-CD70 fusion protein comprising a single amino acid linker between the PD1 and the CD70. Also there is provided a PD1-CD70 fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-CD70 fusion protein, host-cells expressing the PD1-CD70 fusion protein and methods of use thereof.

Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

Disclosed herein, in certain embodiments, are recombinant myxoma viruses (MYXVs) and nucleic acid constructs encoding the recombinant MYXVs. In some embodiments, the MYXVs are engineered to inactivate or attenuate an activity or expression level of an M153 protein. In some embodiments, the MYXVs are engineered to express one or more transgenes such as a tumor necrosis factor (TNF), interleukin-12 (IL-12), or decorin. Also disclosed herein, in certain embodiments, are methods of using the MYXVs. Some embodiments include providing a MYXV as described herein to a subject in need thereof.

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.