Compositions and methods for treatment of non-hodgkins lymphoma
The present invention provides recombinant peptides comprising a B cell receptor (BCR) or a fragment thereof, nucleotide molecules encoding same, and vaccines and vectors comprising same; and methods of treating, inducing an immune response against, inducing a regression of, and suppressing a formation of a lymphoma, comprising administering same. The present invention also provides methods of inducing a humoral immune response in an animal against an antigen, comprising administering to the animal a fusion peptide comprising an LLO protein or fragment thereof fused to the antigen.
1. A method of inducing an immune response against a B cell lymphoma in a subject, comprising administering a pharmaceutical composition comprising a fusion polypeptide comprising a fragment of a listeriolysin O (LLO) protein and an antigen, wherein said fragment of an LLO protein is chemically conjugated to said antigen, wherein said antigen is a fragment of a B cell receptor (BCR) comprising the idiotype of said BCR, and wherein said fragment of an LLO protein is an N-terminal fragment comprising the amino acid sequence set forth in SEQ ID NO: 25 or an N-terminal LLO-detox fragment comprising the amino acid sequence set forth in SEQ ID NO: 41.
2. The method of claim 1 , wherein said fragment of a BCR is a single chain fragment of the variable regions (scFV) of said BCR.
3. The method of claim 1 , wherein said fragment of a BCR is a 38C13 idiotype of said BCR.
4. The method of claim 3 , wherein said 38C13 idiotype comprises SEQ ID NO: 48.
5. The method of claim 1 , wherein said B cell lymphoma comprises said idiotype.
6. A recombinant Listeria, comprising said fusion polypeptide of claim 1 .
7. A method of inducing an immune response against a B cell lymphoma in a subject, wherein said method comprises administering an isolated polypeptide vaccine mixture, comprising a fragment of a listeriolysin (LLO) protein and an antigen, wherein said antigen is either
a. a B cell receptor (BCR); or
b. a fragment of a BCR comprising the idiotype of said BCR;
and wherein said fragment of an LLO protein is an N-terminal fragment comprising the amino acid sequence set forth in SEQ ID NO: 25 or an N-terminal LLO-detox fragment comprising the amino acid sequence set forth in SEQ ID NO: 41.
8. The method of claim 7 , wherein said fragment of a BCR is a single chain fragment of the variable regions (scFV) of said BCR.
9. The method of claim 7 , wherein said fragment of a BCR is a 38C13 idiotype of said BCR.
10. The method of claim 9 , wherein said 38C13 idiotype comprises SEQ ID NO: 48.
11. The method of claim 7 , wherein said B cell lymphoma comprises said idiotype.
12. The method of claim 1 , wherein said immune response treats a B cell lymphoma in said subject.
13. The method of claim 7 , wherein said immune response treats a B cell lymphoma in said subject.
14. The method of claim 1 , wherein said immune response induces the regression of a B cell lymphoma in said subject.
15. The method of claim 7 , wherein said immune response induces the regression of a B cell lymphoma in said subject.
16. The method of claim 1 , wherein said immune response overcomes immune tolerance to a B cell lymphoma in said subject.
17. The method of claim 7 , wherein said immune response overcomes immune tolerance a B cell lymphoma in said subject.
18. The method of claim 1 , wherein said immune response reduces the incidence of relapse of a B cell lymphoma in said subject.
19. The method of claim 7 , wherein said immune response reduces the incidence of relapse of a B cell lymphoma in said subject.
20. The method of claim 1 , wherein said immune response suppresses a formation of a B cell lymphoma in said subject.
21. The method of claim 7 , wherein said immune response suppresses a formation of a B cell lymphoma in said subject.
22. The method of claim 1 , wherein said immune response reduces remission of a residual B cell lymphoma disease in said subject.
23. The method of claim 7 , wherein said immune response reduces remission of a residual B cell lymphoma disease in said subject.
24. The method of claim 1 , wherein said immune response induces a humoral response against a B cell lymphoma in said subject.
25. The method of claim 1 , further comprising inducing an antiserum.
26. A method of producing a monoclonal antibody, comprising inducing a humoral immune response in an animal according to the method of claim 1 .
27. The method of claim 7 , wherein said immune response induces humoral response against a B cell lymphoma in said subject.
28. The method of claim 7 , further comprising inducing an antiserum.
29. A method of producing a monoclonal antibody, comprising inducing a humoral immune response in an animal according to the method of claim 7 .