Molecular determinants of cancer response to immunotherapy are described.

The present application provides methods for treating exudative maculopathies including methods based on rapid centrifugal fluidic immunoassays.

Compositions and methods are provided for reducing the mammalian transmission of Streptococcus pneumoniae (S. pneumoniae) through the administration to mammalian subjects of vaccine compositions comprising at least one immunogenic polypeptide comprising a S. pneumoniae protein or a fragment or variant thereof that is required for or involved in transmission of the bacteria between mammalian hosts. These vaccine compositions also serve to reduce the incidence rate of at least one invasive disease caused by S. pneumoniae. Methods are also provided for identifying additional genetic factors involved in mammalian transmission of S. pneumoniae.

The invention relates to (i) an angiogenesis gene signature and (ii) a monocytic myeloid-derived suppressor cell (mMDSC) gene signature that are each predictive of patient response to treatment with a PD-1 antagonist, wherein the angiogenesis signature comprises five or more genes. More specifically, a lower angiogenesis score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Similarly, a lower mMDSC score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Also provided are methods of treating a cancer patient with a PD-1 antagonist that were identified as either (i) positive for the angiogenesis gene signature biomarker of the invention or (ii) positive for the mMDSC gene signature biomarker of the invention.

A method for generating an immune score, the method comprising the steps of: (i) determining a qualitative and/or quantitative assessment of tumor infiltrating lymphocytes in a sample; (ii) determining a qualitative and/or quantitative assessment of T-cell receptor signaling in the sample; (iii) determining a qualitative and/or quantitative assessment of mutation burden in the sample; (iv) generating, using a predictive algorithm, an immune score based on the determined qualitative and/or quantitative assessment of tumor infiltrating lymphocytes, the determined qualitative and/or quantitative assessment of T-cell receptor signaling, and the determined qualitative and/or quantitative assessment of mutation burden.

Compositions and methods for enhancing antigen-specific immunity in a subject are provided. Pharmaceutical compositions including an effective amount of an immuno-stimulatory cardiolipin as an adjuvant in combination with an antigen and methods of use thereof for stimulating protective immunity to the antigen in a subject are provided. Administration of the combination of the antigen and cardiolipin adjuvant is effective to enhance antigen-specific immunity in a subject to a greater degree than administering to the subject the same amount of the antigen alone. The active agents can be administered together or separately. In preferred forms the cardiolipin is cardiolipin species (C18:2).sub.4. In preferred forms the antigen is formulated as a vaccine, such as an influenza vaccine. A preferred amount by weight of each reagent is about 10-40% cardiolipin to about 90-60% antigen(s), inclusive.

Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

The present invention relates to compositions and methods for cancer therapy, including but not limited to, therapies that utilize cancer biomarkers. In particular, the present invention relates to compositions and methods for the prediction of a subject's response to cancer therapies.

Methods for enhancing the efficacy, safety, and/or tolerability of a grass allergen-specific subcutaneous immunotherapy (SCIT) regimen in a subject having a grass allergy are provided. Methods comprising administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody or antigen-binding fragment thereof, are provided.

The present invention relates to methods of treating a patient having a disorder associated with BCMA expression (e.g. BCMA-expressing B-cell cancers, such as multiple myeloma) using dose-escalation dosing regimens with multispecific (e.g. bispecific) antibodies that bind to CD3 and BCMA.