Provided are methods of treating a FGF19-mediated cancer or tumor in a subject by administering to the subject an anti-IL-6 antibody or an anti-IL-6 receptor antibody or an inhibitor of STAT3/JAK signaling pathway, and pharmaceutical compositions relating thereto.

The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells expressing anti CD19 CAR PBCAR0191, anti CD20 CAR PBCAR20A or anti BCMA CAR PBCAR269A.

Disclosed herein are methods, compositions, and kits useful to enhance an immune response against an antigen and to improve vaccine efficacy. The disclosed methods, compositions, and kits may be utilized to improve vaccine immunogenicity and enhance immune protection following subsequent antigen challenges. In some embodiments, the methods include co-administering a blocker of the IFN-I pathway with an antigen that is used as part of a vaccine, such as a viral vaccine.

The disclosure describes HCMV ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive proliferation of mature activated CD4+ T cells associated with the human T-cell lymphotropic virus type I (HTLV-I). The inventors performed an integrated genomic analysis of a retrospective cohort of 62 ATL patients mainly originating from Africa and the Caribbean area. In particular, they identified a subset of mutations in the TCR/NF-KB pathway (PLCG1, CARD11, PRKCB, CBLB, IRF4, CSNK1A1, FYN, RHOA, VAV1). Furthermore, the inventors investigated the effects of an anti-CD3 antibody (OKT3) exposure on 4 ATL samples including 2 cases harboring CARD 11 and PRKCB gain of function alterations and 2 cases without any TCR pathway mutation. The data suggest that ATL harboring TCR pathway mutations clearly responded to anti-CD3 (FIG. 1B, red+OKT3) and died by apoptosis possibly by a mechanism resembling AICD. Importantly, these TCR-pathway/NFKB mutated patients also showed poorer outcome as compared to unmutated cases. Accordingly, the present invention relates to a method of treating adult T-cell leukemia/lymphoma (ATL) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an anti-CD3 antibody.

A pharmaceutical composition comprising at least two peptides of from 15 to 60 amino acids in length, selected from peptides comprising a sequence of at least 15 contiguous amino acids of one of the sequences shown in SEQ ID NOs: 1 to 4 or of a sequence having at least 80% identity to one of the sequences shown in SEQ ID NOs: to 4, wherein each peptide comprises at least one CD8+ T-cell epitope and/or at least one CD4+ T-cell epitope and wherein each peptide elicits a response in peripheral blood mononuclear cells (PBMC) from at least one chronically infected HBV individual in an 10 in vitroassay.

The present invention relates to uses of inhibitors of human Growth and Differentiation Factor 15 (GDF-15), and to combined uses of such inhibitors with immune checkpoint blockers, in the treatment of solid cancers.

The disclosure provides methods of treating inflammation without inducing immune suppression. The method comprises administering a therapeutically effective amount of an IL-6 antagonist at a dose sufficient to reduce inflammation without causing immune suppression.

Aspects of the invention relate to methods for producing an antigen-specific immune response to human cytomegalovirus (hCMV) in a subject by administering mRNA vaccines comprising hCMV antigenic polypeptides gH, gL, UL128, UL130, UL131 A and gB formulated in lipid nanoparticles, wherein the antigen-specific immune response to hCMV results in neutralizing antibodies that have i) a geometric mean titer of at least 3-fold against epithelial cell infection or ii) a geometric mean ratio of 9-41 against epithelial cell infection or iii) a geometric mean ratio of 4-8-fold against fibroblast infection.

The invention provides methods for the treatment of cancer. The invention also provides a method for identifying a subject whose cancer is likely to respond to combination ICOS agonist and PD1 antagonist therapy, the method comprising determining the RNA signature (Table 1) score of a sample of the cancer of the subject.