Activation of human antigen-presenting cells through dendritic cell lectin-like oxidized LDL receptor-1 (LOX-1)
The present invention includes compositions and methods for targeting the LOX-1 receptor on immune cells and uses for the anti-LOX-1 antibodies.
1. A method for increasing the effectiveness of antigen presentation by a LOX-1-expressing antigen presenting cell comprising the steps of:
providing a human antigen presenting cell;
contacting the antigen presenting cell with an anti-human LOX-1-specific antibody capable of increasing antigen presentation by the antigen presenting cell, wherein the antigen presenting cell is activated;
activating in vitro the antigen presenting cell with GM-CSF and IL-4 or Interferon alpha; and
increasing the surface expression of CD86 and HLA-DR on the antigen presenting cell through the contact with the LOX-1-specific antibody.
2. The method of claim 1 , wherein the antigen presenting cell comprises an isolated dendritic cell, a peripheral blood mononuclear cell, a monocyte, a myeloid dendritic cell and combinations thereof.
3. The method of claim 1 , wherein the antigen presenting cell comprises an isolated dendritic cell, a peripheral blood mononuclear cell, a monocyte, a B cell, a myeloid dendritic cell and combinations thereof that have been cultured in vitro with interferon alpha, an antigen or a combinations thereof.
4. The method of claim 1 , wherein the antigen presenting cell comprises a human dendritic cell that has been contacted with Interferon alpha to activate the dendritic cell, wherein the activated dendritic cell increases the surface expression of CD80.
5. The method of claim 1 , wherein the antigen presenting cell comprises a dendritic cell and the activated dendritic cell increases the secretion of IL-12p40, MCP-1, IL-8, TNFa, IL-6, MIP-1a, and IL-1b.
6. The method of claim 1 , wherein the antigen presenting cell comprises a dendritic cell and increases the activation in conjunction with signaling through CD40.
7. The method of claim 1 , wherein the antigen presenting cell comprises a dendritic cell having an increase in co-stimulatory activity.
8. The method of claim 1 , wherein the human antigen presenting cell comprises a dendritic cell contacted with the LOX-1-specific antibody or fragment thereof have a change in expression profile in one or more genes selected from ALCAM; CSF2RA; CCL17; CCL22; PRG2; CD1B; TGFA; MAPSK14; NCAM1; TNFRSF18; BCL2L1; CD1C; FAIM; ITGAX; CCL24; CD1A; MRC1; PRKCB1; MAPK13; SPINK1; CCNL1; MAPK8IPS; CDGG; MAP4K4; SLATS; TFRC; IL18; NFATCS; TNFSF15; BCL2A1; LILRAS; CDG0; CCL5; CCL20; IL17RB; IL12B; TNIPS; PTGS2; TNFRSPGS; ILSRA; TNF; and CXCL1.