The present invention relates to compositions and methods for treating cancer by targeting the Activin signaling pathway. In certain embodiments, combining Activin blockade with immunomodulation alters regulatory T (Treg) cell-mediated immune regulation and treats cancer.

The instant disclosure provides antibodies that specifically bind to CD137 (e.g., human CD137) and increases CD137 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, bladder cancer. The invention provides methods of treating bladder cancer, methods of determining whether a patient suffering from bladder cancer is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from bladder cancer to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from bladder cancer, based on somatic mutation levels of genes of the invention (e.g., somatic mutation levels in a tumor sample obtained from the patient).

The present invention provides methods for stimulating an immune response to an antigen comprising administering to an individual, an anucleate cell-derived vesicle comprising an antigen and/or an adjuvant. In some embodiments, the anucleate cell-derived vesicle comprising the antigen and/or adjuvant is generated by passing a cell suspension containing an input anucleate cell through a constriction, wherein the constriction deforms the input anucleate cell thereby causing a perturbation of the cell to form an anucleate cell-derived vesicle such that an antigen and/or an adjuvant enters the anucleate cell-derived vesicle. In some embodiments, the anucleate cell-derived vesicle comprising the antigen and/or adjuvant is delivered to an individual and the antigen is delivered to and processed in an immunogenic environment to treat a disease, prevent a disease, and/or vaccinate an individual against an antigen.

The invention is based on the discovery that unmodified mRNA encapsulated in a liposome that is preferentially directed to the liver is particularly effective at inducing immune tolerance in a subject and avoids the need for co-administering an immune regulator (either separately or in form of an mRNA encoding the immune regulator). The invention therefore provides methods for inducing immune tolerance to one or more peptides, polypeptides or proteins in a subject in need thereof, wherein said method comprises administering to the subject one or more mRNAs, each mRNA comprising a 5′UTR, a coding region and a 3′UTR, wherein the one or more coding regions of the one or more mRNAs encode the one or more peptides, polypeptides or proteins, wherein said one or more mRNAs are encapsulated in one or more liposomes, wherein upon administration the one or more liposomes are preferentially delivered to the liver of the subject, wherein the nucleotides of the one or more mRNAs are unmodified.

The present disclosure provides T-cell modulatory antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding T-cell modulatory antigen-presenting polypeptides of the present disclosure, as well as cells genetically modified with the nucleic acids. A T-cell modulatory antigen-presenting polypeptide of the present disclosure is useful for modulating activity of a T cell. 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 autoimmune disorders.

The present disclosure provides T-cell modulatory antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding T-cell modulatory antigen-presenting polypeptides of the present disclosure, as well as cells genetically modified with the nucleic acids. A T-cell modulatory antigen-presenting polypeptide of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides methods of modulating activity of a T cell.

A compound for the sequestration of undesirable antibodies (e.g. related to an autoimmune disease) in a patient. The compound includes an inert biopolymer scaffold and at least a first peptide n-mer of the general formula P(—S—P).sub.(n-1) and a second peptide n-mer of the general formula P(—S—P).sub.(n-1); wherein, independently for each occurrence, P is a peptide with a sequence length of 2-13 amino acids and S is a non-peptide spacer, wherein, independently for each of the peptide n-mers, n is an integer of at least 1, wherein each of the peptide n-mers is bound to the biopolymer scaffold. Also provided are pharmaceutical compositions including the compound, as well as a method of sequestering one or more antibodies present in an individual and a method of inhibiting an immune reaction to a treatment with an active agent.

The present invention relates generally to an immunotherapeutic composition. More particularly, the present invention relates to an immunotherapeutic composition which interacts immunologically with T lymphocytes in subjects having peanut allergy or allergy to other tree nuts. This composition is preferably immunointeractive with T cells in subjects having an allergy to the Ara h 1 and/or Ara h 2 allergens. The composition of the present invention is useful in the therapeutic or prophylactic treatment of conditions characterised by an aberrant, inappropriate or otherwise unwanted immune response to peanut, Ara h 1 and/or Ara h 2 or derivative or homologue thereof.

Isolated MHC-derived human peptides, particularly an isolated MHC-derived human peptide including a SDVGE-X-R (SEQ ID NO: 13) 7 amino acids motif that is selected from: NQEESVRFDSDVGEFR (Hpep 1-SEQ ID NO:1), NREEYARFDSDVGEFR (Hpep2-SEQ ID NO:2), NREEYVRFDSDVGEYR (Hpep4-SEQ ID NO:4) and any peptide with a length of 16 amino acids including the SDVGE-X-R (SEQ ID NO: 13) motif and having an amino acid sequence with at least 80, 85, 86, 87, 88, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity with SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 4. Also, the use of these peptides in methods for inducing an immune tolerance, for preventing or reducing transplant rejection or graft versus host disease (GVHD), and in methods for isolating and expanding a population of CD8.sup.+CD45RC.sup.low Tregs or for expanding a population of CD8.sup.+CD45RC.sup.low Tregs and stimulating its immunosuppressive activity.