The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions.

The present invention relates to Shiga toxin effector polypeptides with reduced antigenic and/or immunogenic potential. Immunogenicity can be a limitation for the repeated administration to mammals of proteins and polypeptides derived from Shiga toxins. The Shiga toxin effector polypeptides of the present invention have uses as components of therapeutics, diagnostics, and immunization materials. The cytotoxic proteins of the present invention have uses for selective killing of specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, immune disorders, and microbial infections. The proteins of the present invention also have uses for detecting specific cell types, collecting diagnostic information, and monitoring the treatment of a variety of diseases, such as, e.g., cancers, immune disorders, and microbial infections.

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

Provided herein are compositions comprising recombinant mammalian cells that express recombinant T cell rectors with specificity against EBV or CMV peptide:MHC antigens. Also provided are therapeutic methods of using the recombinant mammalian cells as cell therapies against viral infections.

Disclosed herein are antibodies or immunogenic fragments thereof that specifically bind to Epstein-Barr virus (EBV) glycoprotein 350 (gp350) or 220 or one or more epitopes of EBV gp350 and neutralize EBV infection. Also disclosed are immunogenic peptides comprising one or more gp350 epitopes, EBV antibody-small molecule conjugates and pharmaceutical compositions comprising the antibody or an immunogenic fragment thereof, one or more epitopes of EBV gp350, one or more immunogenic peptides, or the EBV antibody-small molecule conjugate. The antibodies, epitopes, immunogenic peptides, conjugates, and pharmaceutical compositions can be used to treat or prevent EBV infections and EBV-associated conditions and diseases.

The invention relates to a method for generating an antibody binding to a cell surface protein of interest, the method comprising the following steps: (a) providing a non-human cell which does not express the endogenous form of the cell surface protein of interest but expresses an exogenous form of the cell surface protein of interest comprising at least one human segment; (b) immunization of a non-human animal with the cell line provided in step (a); (c) generation of hybridomas from the immunized non-human animal of step (b); (d) screening for an antibody that binds to the cell surface protein of interest by contacting the antibodies secreted by the hybridomas of step (c) with human cells which do not express the endogenous form of the cell surface protein of interest but express an exogenous form of the cell surface protein of interest comprising at least one human segment.

Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Epstein Barr Virus infection in mammals, and methods of using those compositions of matter for the same are disclosed. Also disclosed are proteins, referred to as anti-gp350 antibody probes, and anti-gp350 B-cell probes, that maintain the epitope structure of the CR2-binding region of gp350, but do not bind CR2.

A novel fusion protein to overcome the current difficulties related to application of monoclonal antibodies in disease treatment and in other fields, particularly those requiring ADCC, e.g. for depletion of tumor cells, virally-infected cells, or immune-modulating cells, etc. One example of the fusion protein is an extracellular domain of a high-affinity variant of human CD 16 A fused to an anti-CD3 antibody or its antigen-binding fragment thereof that specifically binds to an epitope on human CD3 or a fragment thereof.

Described are immunoglobulins provided with a toxic moiety, comprising at least an immunoglobulin variable region that specifically binds to an MHC-peptide complex preferentially associated with aberrant cells. These immunoglobulins provided with a toxic moiety may be used in selectively modulating biological processes. These immunoglobulins provided with a toxic moiety are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrations, such as cancers and autoimmune diseases.

The invention provides improved non-human vertebrates and non-vertebrate cells capable of expressing antibodies comprising human variable region sequences. The present invention is directed to the provision of long HCDR3s from non-human vertebrates and cells. The present invention is also directed to the provision of novel V, D and J pairings in immunoglobulin heavy and light chain loci. Novel, biased antibody diversities and potentially expanded diversities are provided. The invention also provides for novel and potentially expanded diversity or diversity that is biased towards variable gene usage common to antibodies useful for treating and/or preventing certain diseases or conditions, such as infectious diseases. The invention also provides methods of generating antibodies using such vertebrates, as well as the antibodies per se, therapeutic compositions thereof and uses.