Embodiments relate to peptide antagonists of γc-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting γc-cytokine activity involve raising neutralizing antibodies against each individual γc-cytokine family member/receptor subunit. However, success has been limited and often multiple γc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.

The disclosure provides, among other things, methods and uses for treating a disease or disorder, particularly tumors of a cancer patient, comprising conjointly administering effective amounts of a STING agonist, a cytokine, and an optional immune checkpoint inhibitor to the patient, wherein the STING agonist or the cytokine is intratumorally administered to the patient.

The disclosure provides, among other things, methods and uses for treating a disease or disorder, particularly tumors of a cancer patient, comprising conjointly administering effective amounts of a STING agonist, a cytokine, and an optional immune checkpoint inhibitor to the patient, wherein the STING agonist or the cytokine is intratumorally administered to the patient.

Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.

The present invention relates to a bifunctional molecule comprising an anti-PD-1 antibody and IL-7 and its uses.

The present invention provides a combination therapy of genetically modified vaccinia virus (particularly oncolytic vaccinia virus) and another cancer therapy for use in treating cancer, and a pharmaceutical composition and a combination kit for use in the therapy. More specifically, the invention provides a therapy with vaccinia virus containing a polynucleotide encoding interleukin-7 (IL-7) and a polynucleotide encoding interleukin-12 (IL-12) in combination with an immune checkpoint inhibitor, and a pharmaceutical composition and a combination kit for use in the therapy.

The present application provides GPC2-specific antibodies and antigen binding fragments thereof. A chimeric antigen receptor (CAR) that specifically binds glypican-2 (GPC2) comprising a GPC2-specific antibody, a transmembrane domain, and an intracellular signaling domain. T cells comprising the disclosed CAR constructs can be used for cancer immunotherapy.

Methods and compositions are provided for delivery of a polynucleotide encoding a gene of interest, typically an antigen, to a dendritic cell (DC). The virus envelope comprises a DC-SIGN specific targeting molecule. The methods and related compositions can be used to treat patients suffering from a wide range of conditions, including infection, such as HIV/AIDS, and various types of cancers.

A method of treating a metastatic lesion that presents a peptide containing SLLQHLIGL (SEQ ID NO: 310) on a cell surface, including selecting a patient having a metastatic lesion and administering to the patient a composition containing recombinant T lymphocytes or activated T lymphocytes that express a T cell receptor, or a functional fragment thereof, that is reactive with, or binds to, an MHC ligand containing SLLQHLIGL (SEQ ID NO: 310).

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5), in which the peptide is in a complex with an MHC molecule.