Treatment of follicular lymphomas using inhibitors of the LT pathway
View Patent ↗Therapeutic uses of inhibitors of the Lymphotoxin Pathway to treat tumors, specifically to treat follicular lymphomas.
1. A method for altering the survival or maintenance of a follicular dendritic cell in a subject having a B cell lymphoma comprising administering an amount of a composition comprising a soluble lyraphotoxin-beta receptor (LT-beta-R) and a pharmaceutically acceptable carrier, such that the survival or maintenance of a follicular dendritic cell is altered, and further comprising administering either radiation or at least one chemotherapeutic agent to the subject.
2. The method of claim 1 , wherein altering the survival or maintenance of a follicular dendritic cell comprises inhibiting the survival of the follicular dendritic cell.
3. The method of claim 1 , wherein altering the survival or maintenance of a follicular dendritic cell comprises disrupting the function of a mature follicular dendritic cell.
4. The method of claim 1 , wherein altering the survival or maintenance of a follicular dendritic cell comprises disrupting germinal center function.
5. The method of claim 1 , wherein the subject is a mammal.
6. A method for altering the survival or maintenance of a follicular dendritic cell in a human subject having a B cell lymphoma, the method comprising administering to the subject a pharmaceutical composition comprising a polypeptide that comprises a salable, ligand-binding domain of human lymphotoxin-beta receptor (LT-beta-R) fused to a human IgG1 Fc domain, such that the survival or maintenance of a follicular dendritic cell in a human subject is altered.
7. The method of claim 1 , further comprising administering to said subject a bone marrow transplant.
8. The method of claim 1 , wherein the composition comprises a soluble LT-beta-R fused to one or more heterologous protein domains.
9. The method of claim 8 , wherein the heterologous protein domain is selected from the group consisting of an immunoglobulin, a serum albumin, a lipoprotein, an apolipoprotein, and a transferrin.
10. The method of claim 8 , wherein the heterologous protein domain is a human immunoglobulin Fc domain.
11. The method of claim 1 , wherein the soluble LT-beta-R comprises a ligand binding domain that can selectively bind to a surface LT ligand.
12. The method of claim 1 , wherein the soluble LT-beta-R comprises an extracellular domain of LT-beta-R.
13. The method of claim 1 , wherein the soluble LT-beta-R is human LT-beta-R.
14. The method of claim 13 , wherein the soluble LT-beta-R further comprises a human immunoglobulin Fc domain.
15. The method of claim 14 , wherein the human immunoglobulin Fc domain is IgG1.
16. The method of claim 1 , wherein the soluble LT-beta-R comprises SEQ ID NO:1, or a functional fragment thereof.
17. The method of claim 5 or 6 , wherein the subject is a human.
18. The method of claim 6 , wherein the soluble, ligand-binding domain of human LT-beta-R comprises the sequence of SEQ ID NO:1, or a functional fragment thereof.
19. A method for altering the survival and maintenance of follicular dendritic cells in a subject having a B cell lymphoma comprising administering an inhibitor of the interaction between LT-beta and its receptor and further comprising administering either radiation or at least one chemotherapeutic agent to the subject.
20. The method of claim 19 , wherein the inhibitor comprises a soluble lymphotoxin-beta receptor (LT-beta-R).