Anti-Fn amyloid-like FadA antibodies and compositions are provided and methods of treating cancers, including pancreatic and colorectal, and periodontal diseases. Methods include preventing, reducing development, or treating disease in a subject in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an agent which inhibits or blocks an amyloid-like FadA secreted from Fusobacterium nucleatum (Fn).
1. An antibody which binds Fusobacterium nucleatum amyloid-like adhesin A (Fn amyloid-like FadA), or an Fn amyloid-like FadA-binding fragment thereof, or a Fn amyloid-like FadA-binding fusion protein, comprising:
a heavy chain comprising:
CDR1 having the sequence GYTFTTYW (SEQ ID NO:1);
CDR2 having the sequence INPNTDYT (SEQ ID NO:2);
CDR3 having the sequence ARSGYFGSRYYFDY (SEQ ID NO:3);
and either
a light chain comprising:
CDR1 having the sequence QSLANSYGNTY (SEQ ID NO:4);
CDR2 having the sequence GIS (SEQ ID NO:5);
CDR3 having the sequence LQGTHQPPT (SEQ ID NO:6);
or
a light chain comprising:
CDR1 having the sequence QDINKY (SEQ ID NO:7);
CDR2 having the sequence YTS (SEQ ID NO:8);
CDR3 having the sequence LQYDYLLH (SEQ ID NO:9).
2. The antibody, Fn amyloid-like FadA-binding fragment thereof, or Fn amyloid-like FadA-binding fusion protein of claim 1 ,
wherein the light chain comprises:
CDR1 having the sequence QSLANSYGNTY (SEQ ID NO:4);
CDR2 having the sequence GIS (SEQ ID NO:5); and
CDR3 having the sequence LQGTHQPPT (SEQ ID NO:6.
3. The antibody, Fn amyloid-like FadA-binding fragment, or Fn amyloid-like FadA-binding fusion protein of claim 1 , comprising framework regions of a light chain and/or a heavy chain which are human framework regions or have 85% or more sequence identity therewith.
4. The antibody of claim 1 , wherein the antibody is a humanized antibody.
5. The antibody or Fn amyloid-like FadA-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment thereof has a human sequence Fc region or has 85% or more sequence identity therewith.
6. The antibody or Fn amyloid-like FadA-binding fragment of claim 1 , wherein the antibody or fragment thereof is chimeric.
7. The antibody or Fn amyloid-like FadA-binding fragment of claim 1 , wherein the antibody is a monospecific antibody comprising two heavy chains of identical sequence and two light chains of identical sequence.
8. The antibody of claim 1 .
9. The antibody of claim 1 , which is a monoclonal antibody.
10. The antibody of claim 1 , wherein the antibody is an IgG1(λ) or an IgG2(λ) or an IgG4.
11. The Fn amyloid-like FadA-binding fragment of an antibody of claim 1 .
12. The Fn amyloid-like FadA-binding fragment of claim 1 , which is an Fab fragment, an Fab′ fragment, or an F(ab)′ fragment.
13. The Fn amyloid-like FadA-binding fusion protein of claim 1 , which is a single chain variable fragment (scFv).
14. A pharmaceutical composition comprising an antibody which binds Fn amyloid-like FadA, or a Fn amyloid-like FadA-binding fragment thereof, or a Fn amyloid-like FadA-binding fusion protein, of claim 1 and a carrier.
15. A nucleic acid encoding a heavy chain as set forth in claim 1 .
16. A nucleic acid encoding a light chain as set forth in claim 2 .