Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Compositions comprising memory T cell Targeting Constructs comprising an anti-T cell antibody or antigen-binding portion thereof linked to a near-infrared photoactivated cytotoxin, e.g., a photoactive adduct of an infrared dye, and methods of use thereof for reducing numbers of pathogenic T cells selectively in peripheral tissues e.g., for treating inflammatory and autoimmune diseases.

An object of the present invention is to provide an antibody composition, which more selectively exhibits an effector function against a target cell coexpressing two types of antigens that are different from each other and damages the target cell, and also can maintain affinity for the individual target antigens sufficiently high. The present invention relates to an antibody composition against a first antigen and a second antigen that are different from each other, composed of a first IgG half-molecule and a second IgG half-molecule.

The tissue microenvironment is a critical factor to disease mechanism and therapeutic efficiency. Provided here is an imaging platform, methods, and kits which enable measurement of tens of parameters simultaneously within a single tissue, with the potential to reveal unique and important biological associations related to the spatial dimension. The sensitivity of the platform, methods, and kits described herein extends to measure low level markers which can be important for tracking disease progression, diagnosing disease, or both.

A method for inducing an immune response against HIV in a subject includes the step of preparing an HIV-1 gp120 envelope protein coding sequence particle having an N425K mutation, introducing the HIV-1 gp120 protein coding sequence particle having an N425K mutation into an expression construct using yeast homologous recombination, transfecting a cell with the expression construct, wherein the HIV-1 particle is secreted by the cell, and administering the secreted HIV-1 particle and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 particle stimulates an immune response in the subject.

Conversation user interfaces that are configured for virtual assistant interaction may include contextual interface items that are based on contextual information. The contextual information may relate to a current or previous conversation between a user and a virtual assistant and/or may relate to other types of information, such as a location of a user, an orientation of a device, missing information, and so on. The conversation user interfaces may additionally, or alternatively, control an input mode based on contextual information, such as an inferred input mode of a user or a location of a user. Further, the conversation user interfaces may tag conversation items by saving the conversation items to a tray and/or associating the conversation items with indicators.

Antigen binding constructs that bind to CD4, for example antibodies, including antibody fragments (such as scFv, minibodies, and cys-diabodies) that bind to CD4, are described herein. Methods of use are described herein.

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-β)) and regulatory T cells and/or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

The present invention provides a method of treating cancer with a combination of IL-2 and an integrin-binding-Fc fusion protein. The methods of the invention can be applied to a broad range of cancer types.

The present invention relates in a first aspect to a method for the stratification of a therapeutic regimen of a subject afflicted or suspected to be afflicted with an immune regulatory antibody-mediated disease based on the immune status of said subject, the method is based on determining the level or amount of expression of PD-1 in a predetermined subset of B-cells, thus, reflecting the immune tolerance status against an immune tolerance inducing compound of said subject. In addition, a method for monitoring of the development or progress of a treatment in a subject based on an administration of immune-tolerance-inducing compound containing antigenic epitopes recognized by the B-cells producing these antibodies. Further, a method for determining the risk of developing antibody-producing B-cells based failure of immune tolerance induction (ITI) treatment in a subject is provided. Moreover, the use of PD-1 expression as a marker in antibody-mediated disease based on B-cell tolerance status is described. Finally, a kit for use in determining antibody-producing B-cells for determining B-cell tolerance status in a predetermined set of B-cells is described.