The present invention is directed to Fc fusion water soluble GPCR (G-protein coupled receptor) proteins with QTY membrane regions, wherein the amino acids Q (Glutamine), T (Threonine), and Y (Tyrosine), together with other amino acids can form an alpha helical domain that mimics a transmembrane region, and the QTY code conversions render the alpha-helical segment water-soluble. Further disclosed are methods for the preparation QTY Fc receptor and methods of use thereof.

A method for predicting whether a patient diagnosed with a disease, disorder, condition or injury of the CNS is likely to be responsive or non-responsive to treatment with an immune checkpoint modulator is provided, wherein said method comprises determining ex vivo, in a blood sample obtained from the patient, or in a fraction thereof, a biomarker selected from: (a) the level of a monocyte subpopulation expressing CCR2, CD204 or a combination thereof, or CCR2 and a marker selected from igf1, lyve1, Stab-1, Siglec1 and Mrc1, or any combination thereof, (b) the ratio of the level of a monocyte subpopulation (CD14.sup.+ cells) expressing CCR2.sup.highCX3CR1.sup.low to a monocyte subpopulation expressing CCR2.sup.lowCX3CR1.sup.high; (c) the level of a CCR2 agonist; and (d) the level of a CCR2 antagonist.

The present invention pertains to the nanoencapsulation of siRNA and other biologics in phospholipid nanosomes for the improved delivery of siRNA and other biologics to targeted diseased human or animal organs and human or animal cells and apparatus and methods for making the same. In embodiments of the present invention, novel siRNAs were designed to down regulate CCR5 and CD4, based on an analysis of all known alternative transcripts for each gene from both human and monkey (Macaca mulatta) genomes. Embodiments of the present invention feature supercritical, critical and near critical fluids. Embodiments of the present invention also pertain to down regulation of CXCR4 receptor and targeting of nanosomes containing specific siRNA sequences to cells expressing those receptors on the cell surface by coating them with specific ligands. These include ligands for the receptors CCR5, CD4 and CXCR4.

The disclosure relates to modified oncolytic viruses. The modified oncolytic viruses of the disclosure comprise modification in the viral genome encoding exogenous nucleic acids to enhance the oncolytic immunotherapy by remodeling the tumor microenvironment and with enhanced systemic delivery. The disclosure further relates to compositions comprising the modified oncolytic viruses, kits containing the same, and methods of using the oncolytic viruses.

The present invention relates to CXCR6-transduced (a) T cell(s) such as (a) CD8+ T cell(s), (a) CD4+ T cell(s), (a) CD3+ T cell(s), (a) γδ T cell(s) or (a) natural killer (NK) T cell(s) for targeted tumor therapy, nucleic acid sequences, vectors capable of transducing such (a) T cell(s), (a) transduced T cell(s) carrying the nucleic acid sequences or vectors of the present invention, methods and kits comprising the nucleic acid sequences or vectors of the present invention. The invention also provides the use of said transduced T cell(s) in a method for the treatment of diseases characterized by CXCL16 overexpression as well as a pharmaceutical composition/medicament comprising (a) transduced T cell(s) expressing the CXCR6 for use in methods of treating diseases characterized by CXCL16 overexpression.

The present invention relates to tools and methods for the generation of antibodies which specifically bind chemokine receptors, such as CC or CXC chemokine receptors. Provided are isolated sulfated polypeptides and conjugates thereof, which can be used for example as antigens or for off target panning to facilitate the generation of anti-human, anti-cynomolgus, and/or anti-mouse chemokine receptor antibodies, e.g. for the generation of antibodies with fully human CDRs and/or other favorable properties for therapeutic use. The present invention furthermore relates to antibodies and conjugates thereof which can be obtained by applying the aforementioned tools and methods. Provided are antibodies specifically binding to human, cynomolgus and/or murine CCR8 with favorable properties for therapeutic use, such as cross-reactive antibodies, fully human antibodies, low internalizing (including non-internalizing) antibodies, and antibodies efficiently inducing ADCC and/or ADCP in Treg cells. Also provided are medical uses of the inventive antibodies or conjugates and/or treatment methods comprising the administration of these antibodies to a patient or subject, either alone or in combination. Biomarkers, stratification methods and diagnostic methods are finally provided to predict or evaluate responsiveness to anti-CCR8 antibody monotherapy or combination therapy. The invention furthermore provides tools and methods for producing the foregoing antibodies, pharmaceutical compositions, diagnostic uses of the antibodies, and kits with instructions for use.

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

This disclosure provides a modified oncolytic virus that can contain modifications in the viral genome and exogenous nucleic acids coding for proteins. The modified oncolytic virus can be utilized as a platform vector for systemic delivery.

The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

The present invention relates to a chemokine-selective CXCR4 ectodomain-derived (poly)peptide comprising or consisting of a first peptide of (X1)(X2)(X3)(X4)(X5)WYFGNF(X6)(X7)(X8) (SEQ ID NO: 1) linked via a linker to a second peptide of (Y1)(Y2)(Y3)(Y4)(Y5)D(Y6)FY(Y7)N(Y8)LW(Y9) (SEQ ID NO: 2), wherein (X1) is present or absent and, if present, is an amino acid, preferably D or A (X2) is present or absent and, if present, is an amino acid, preferably A or G (X3) is present or absent and, if present, is an amino acid, preferably V or A (X4) is present or absent and, if present, is an amino acid, preferably A or G (X5) is present or absent and, if present, is an amino acid, preferably N (X6) is an amino acid, preferably L or A (X7) is an amino acid, preferably C, A or S, more preferably C or A (X8) is an amino acid, preferably K or A (Y1) is present or absent and, if present, is an amino acid, preferably D or A (Y2) is present or absent and, if present, is an amino acid, preferably R or A (Y3) is present or absent and, if present, is an amino acid, preferably Y (Y4) is present or absent and, if present, is an amino acid, preferably I or A (Y5) is present or absent and, if present, is an amino acid, preferably C. A or S, more preferably C or A (Y6) is present or absent and, if present, is an amino acid, preferably D, R or A (Y7) is an amino acid, preferably P or A (Y8) is an amino acid, preferably D or A (Y9) is present or absent and, if present, is an amino acid, preferably V;
and wherein said linker has a length of 0.2 to 5 nm, preferably 1 nm to 5 nm, more preferably 2 to 4 nm, and most preferably about 2.358 nm.