Targeting immunotherapy for amyloidosis
Disclosed are methods and compositions for targeting antibodies to amyloid deposits. For example, amyloid-reactive peptides that bind amyloid deposits are administered to a subject. Antibodies to the amyloid-reactive peptides are then administered to the subject. Upon administration of the antibodies, the amyloid-reactive peptides bind the antibodies and thus pre-target the antibodies to the amyloid deposits. In other examples, an amyloid-reactive fusion peptide contains an epitope of a known antibody. When the fusion peptide is administered to a subject, the fusion peptide binds amyloids in the subject. Administration to the subject of the known antibody that binds the epitope of the fusion peptide then targets the antibody to the amyloid deposit to which the fusion peptide is bound.
1. A method of targeting an amyloid deposit for clearance, comprising: contacting an amyloid deposit of a first amyloid type with an amyloid-reactive fusion peptide, wherein the amyloid-reactive fusion peptide comprises an amino acid that is at least 95% identical to any one of the amino acid sequences set forth as SEQ ID NOS: 1-17 and an epitope; and, contacting the amyloid-reactive fusion peptide with an antibody or functional fragment thereof, wherein the antibody or functional fragment thereof is immunoreactive to a second amyloid type that is different than the first amyloid type and wherein the epitope of the amyloid-reactive fusion peptide directs the antibody or functional fragment thereof to the first amyloid type, thereby targeting the first amyloid deposit for clearance.
2. The method of claim 1 , wherein targeting the first amyloid deposit for clearance results in clearance of the first amyloid deposit.
3. The method of claim 1 , wherein the epitope comprises an 11-1F4 antibody-binding motif.
4. The method of claim 3 , wherein the epitope is at least 95% identical to the amino acid sequence set forth as SEQ ID NO:22 or SEQ ID NO:23.
5. The method of claim 3 , wherein the first amyloid type is AA, AH, ATTR, Aβ2M, ALect2, Wild type TTR, AApoAI, AApoAII, AGel, ALys, Afib, ACys, ACal, AMedin, AIAPP, APro, AIns, APrP, or Aβ amyloid.
6. The method of claim 5 , wherein the second amyloid type is AL amyloid.
7. The method of claim 1 , wherein the amyloid-reactive fusion peptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence set forth as SEQ ID NO:18, SEQ ID NO:19, or SEQ ID NO:20.
8. A method for treating amyloidosis in a subject, comprising: administering to a subject an effective amount of an amyloid-reactive fusion peptide, wherein the amyloid-reactive fusion peptide comprises (i) an amyloid-reactive peptide that is at least 95% identical to any one of the amino acid sequences set forth as SEQ ID NOS: 1-17 and (ii) an epitope fused to the amyloid-reactive peptide; and administering to the subject an effective amount of an antibody or functional fragment thereof that binds the epitope of the amyloid-reactive fusion peptide.
9. The method of claim 8 , wherein binding of the antibody or fragment thereof to the epitope of the amyloid-reactive fusion peptide results in clearance of an amyloid deposit in the subject.
10. The method of claim 8 , wherein the amyloid-reactive peptide of the amyloid-reactive fusion peptide binds to one or more amyloid deposit types comprising AA, AL, AH, ATTR, Aβ2M, ALect2, Wild type TTR, AApoAI, AApoAII, AGel, ALys, ALect2, Afib, ACys, ACal, AMedin, AIAPP, AOro, AIns, APrP, or Aβ.
11. The method of claim 8 , wherein the antibody or functional fragment thereof is reactive to one or more of the fusion peptides having an amino acid sequence set forth as SEQ ID NO:18, SEQ ID NO:19 or SEQ ID NO:20.
12. The method of claim 8 , wherein the epitope is an epitope of an 11-1F4 antibody or functional fragment thereof.
13. The method of claim 12 , wherein the epitope comprises an amino acid sequence set forth as SEQ ID NO:22 or SEQ ID NO:23.
14. The method of claim 12 , wherein the antibody or functional fragment thereof is an 11-1F4 antibody or functional fragment thereof.
15. The method of claim 8 , wherein administering to the subject an effective amount of the antibody or functional fragment thereof results in clearance of an amyloid deposit in the subject.
16. The method of claim 8 , wherein the amyloid-reactive fusion peptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence set forth as SEQ ID NO:18, SEQ ID NO:19 or SEQ ID NO:20.