ILT3 binding molecules and uses therefor
First Claim
1. A binding molecule comprising the amino acid sequence of SEQ ID NO:
- 1.
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Abstract
The present invention provides binding molecules that specifically bind to ILT3, e.g., human ILT3 (hILT3), on antigen presenting cells, such as for example, monocytes, macrophages and dendritic cells (DC), e.g., monocyte-derived dendritic cells (MDDC). The binding molecules of the invention are characterized by binding to hILT3 with high affinity and downmodulating immune responses in vitro, e.g., downmodulating alloimmune responses; the production of inflammatory cytokines by dendritic cells, e.g., monocyte-derived dendritic cells (MDDC); the upregulation of costimulatory molecules by DC, e.g., MDDC; and/or calcium flux in monocytes. In addition, the binding molecules upregulate the expression of inhibitory receptors on dendritic cells, e.g., immature dendritic cells. Surprisingly, these same binding molecules which downmodulate immune responses in vitro, are immunostimulatory in vivo. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof. Methods of using the binding molecules of the invention to detect human ILT3 or to modulate human ILT3 activity, either in vitro or in vivo, are also encompassed by the invention.
87 Citations
43 Claims
- 1. A binding molecule comprising the amino acid sequence of SEQ ID NO:
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2. A binding molecule comprising the amino acid sequence of SEQ ID NO:
- 2.
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3. A binding molecule comprising at least one complementarity determining region (CDR) amino acid sequence selected from the group consisting of:
- SEQ ID NO;
3, SEQ ID NO;
4, and SEQ ID NO;
5. - View Dependent Claims (4, 5)
- SEQ ID NO;
-
6. A binding molecule comprising at least one CDR amino acid sequence selected from the group consisting of:
- SEQ ID NO;
6, SEQ ID NO;
7, and SEQ ID NO;
8. - View Dependent Claims (7, 8)
- SEQ ID NO;
- 9. A binding molecule comprising the CDRs shown in SEQ ID NOs:
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10. A binding molecule comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:
- 1 and further comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO;
2. - View Dependent Claims (11, 12)
- 1 and further comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO;
- 13. A binding molecule that binds to ILT-3 on human monocyte-derived dendritic cells (MDDC) and has a binding constant (Kd) of 0.9×
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27. A method for upmodulating an immune response in a subject, comprising contacting a cell from the subject with an anti-ILT3 antibody that inhibits immune cell activation in vitro.
- 31. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable region comprising the nucleotide sequence of SEQ ID NO:
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32. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable region comprising the nucleotide sequence of SEQ ID NO:
- 10.
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33. An isolated nucleic acid molecule comprising a nucleotide sequence encoding at least one CDR selected from the group consisting of:
- SEQ ID NO;
11, SEQ ID NO;
12, and SEQ ID NO;
13. - View Dependent Claims (34, 35)
- SEQ ID NO;
-
36. An isolated nucleic acid molecule comprising a nucleotide sequence encoding at least one CDR selected from the group consisting of:
- SEQ ID NO;
14 SEQ ID NO;
15 and SEQ ID NO;
16. - View Dependent Claims (37, 38)
- SEQ ID NO;
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39. An isolated nucleic acid molecule comprising the nucleotide sequences shown in SEQ ID NOs:
- 11-16.
Specification