A method for suppression of progress of, suppression of recurrence of and/or treatment of cancer, by administering an Allergin-1 antagonist in a therapy of a cancer patient with insufficient therapeutic efficacy by a tumor immunotherapeutic agent, or a cancer therapy in combination with an anti-cancer drug.

The present disclosure is directed to compositions and methods for the prevention, treatment, and/or functional cure of HIV infection. One aspect of the present disclosure relates to monoclonal antibodies directed against CD4, compositions thereof, and methods employing such compositions for the prevention, treatment, and functional cure of HIV infection.

A method of sensitizing cancer to immunotherapy in a subject in need thereof includes administering to the subject a therapeutically effective amount of a CdK5 inhibitor to suppress immune checkpoint PD-L1.

The invention relates to tolerogenic compositions and methods for the preparation, manufacture and therapeutic use thereof.

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.

The present invention relates to amino acid sequences that are directed against (as defined herein) human cellular receptors for viruses and/or bacteria such as e.g. Nanobodies specifically recognizing hCD4, hCXCR4, hCCR5, hTLR4, human alphaV integrin, human beta3 integrin, human beta1 integrin, human alpha2 integrin, hCD81, hSR-BI, hClaudin-1, hClaudin-6 and hClaudin-9, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. Amino acid sequences of the present invention may be used to prevent human cell entry of HIV, HCV, adenoviruses, hantavirus, herpesvirus, echo-virus 1 and others.

Some aspects of the methods and compositions provided herein relate to the disruption of at least one CD4 gene in a cell, such as a CD4+ T cell. In some embodiments, the disruption comprises use of a CRISPR guide polynucleotide. Some embodiments also include the preparation and use of a cell having at least one disrupted CD4 gene and a chimeric antigen receptor (CAR). Some aspects of the methods and compositions provided herein relate to CARs, such as an anti-CD4 CAR or an anti-CD19 CAR, and use to treat disorders including HIV, acute myeloid leukemia (AML), and acute lymphocytic leukemia (ALL).

Disclosed herein are glycan-modified anti-CD4 monoclonal antibodies with N-linked glycans attached to the variable region. Expression vectors and cell lines useful for the production of such antibodies, and use of such antibodies for HIV prevention and therapy are also disclosed.

The present disclosure provides herein anti-CD4 antibodies or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.

The present invention relates to, among others, an in vitro method of modifying a cell graft containing immune cells comprising the steps of incubating a cell graft containing immune cells with an anti CD4 antibody wherein said incubating is carried out for from 1 minute to 7 days, b) removing unbound antibody from said graft; as well as to corresponding modified grafts and uses. The invention further relates to the modification of antibodies reactive to the CD4 human leukocyte antigen to provide anti-CD4 antibodies that have a reduced number of potential T-cell epitopes but retain the ability to bind to CD4, such as to an anti human CD4-antibody comprising a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL), wherein at least one T cell epitope located outside the CDRs of said immunoglobulin variable domains is removed from said immunoglobulin variable domains. Preferably, the specificity and mode of action of the anti-CD4 antibodies are not affected by the modification(s).