Methods of diagnosing and prognosing hodgkin's lymphoma

• US 8,211,649 B2
• Filed: 03/30/2007
• Issued: 07/03/2012
• Est. Priority Date: 03/31/2006
• Status: Active Grant

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Migone, Thi-Sau, Klein, Jerry L., Oki, Yasuhiro, Younes, Anas
• Primary Examiner(s): Bunner, Bridget E
• Application Number:
  US12/295,572
• Publication Number:
  US 20090221008A1
• Time in Patent Office: 1,922 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61K 51/1021 against cytokines, e.g. growth factors, VEGF, TNF, lymphokines or interferons
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention relates to nucleic acid molecules encoding Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to antibodies or portions thereof that specifically bind Neutrokine-alpha and/or Neutrokine-alphaSV and diagnostic and therapeutic methods using these antibodies. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders using the compositions of the invention.

Claims

1. A method of detecting diagnosing Hodgkin'"'"'s lymphoma comprising:

(a) contacting serum from a patient suspected of having Hodgkin'"'"'s lymphoma with an agent that binds a soluble Neutrokine-α

polypeptide consisting of the amino acid sequence from about amino acid 134 to about amino acid 285 of SEQ ID NO;

2;

(b) measuring the expression level of the soluble Neutrokine-α

polypeptide in the serum; and

(c) comparing the measured expression level of the soluble Neutrokine-α

polypeptide with a standard expression level of the soluble Neutrokine-α

polypeptide that is less than 0.5 ng/ml,

wherein an increase in the expression level of the soluble Neutrokine-α

polypeptide in the serum relative to the standard is indicative of Hodgkin'"'"'s lymphoma, and wherein the agent is selected from the group consisting of;

(i) an anti-Neutrokine-α

antibody; and

(ii) a Neutrokine-α

receptor or a soluble Neutrokine-α

receptor.

2. The method of claim 1, wherein the Neutrokine-α

receptor or soluble Neutrokine-α

receptor is selected from the group consisting of;

(a) transmembrane activator and CAML interactor (TACI);

(b);

B cell maturation antigen (BCMA); and

(c) BAFF-R.

3. The method of claim 1, wherein measuring the expression level of the soluble Neutrokine-α

polypeptide is performed using an assay selected from the group consisting of;

(a) ELISA;

(b) radioimmunoassay;

(c) in situ immunoassay;

(d) Western blot;

(e) agglutination assay; and

precipitation reactions.

4. The method of claim 1, wherein the expression level of the soluble Neutrokine-α

polypeptide in serum is greater than 2.0 ng/ml.

5. The method of claim 1, wherein the expression level of the soluble Neutrokine-α

polypeptide in serum is greater than 2.5 ng/ml.

6. The method of claim 1, wherein the expression level of the soluble Neutrokine-α

polypeptide in serum is greater than 3.0 ng/ml.

7. The method of claim 1, wherein the Hodgkin'"'"'s lymphoma is relapsed Hodgkin'"'"'s lymphoma.

8. A method of prognosing Hodgkin'"'"'s lymphoma comprising:

(a) contacting serum from a patient diagnosed with Hodgkin'"'"'s lymphoma with an agent that binds a soluble Neutrokine-α

polypeptide consisting of the amino acid sequence from about amino acid 134 to about amino acid 285 of SEQ ID NO;

2;

(b) measuring the expression level of the soluble Neutrokine-α

polypeptide in the serum;

(c) measuring at least one additional indicator selected from the group consisting of;

(i) male gender;

(ii) stage 4 disease;

(iii) bulky disease >

7.5 cm;

(iv) high LDH;

(v) high β

2-microglobulin;

(vi) resistance to therapy; and

(vii) shorter failure free survival; and

(d) comparing the measured expression level of the soluble Neutrokine-α

polypeptide with a standard expression level of soluble Neutrokine-α

polypeptide that is less than 0.5 ng/ml,

wherein an increase in the expression level of the soluble Neutrokine-α

polypeptide in the serum relative to the standard is indicative of Hodgkin'"'"'s lymphoma;

wherein the agent is selected from the group consisting of;

(i) an anti-Neutrokine-α

antibody; and

(ii) a Neutrokine-α

receptor or a soluble Neutrokine-α

receptor; and

wherein having at least one additional indicator is indicative of a worse prognosis.

9. The method of claim 8, wherein the Neutrokine-α

receptor or soluble Neutrokine-α

receptor is selected from the group consisting of;

(a) transmembrane activator and CAML interactor (TACI);

(b) B-cell maturation antigen (BCMA); and

(c) BAFF-R.

10. The method of claim 8, wherein measuring the expression level of the soluble Neutrokine-α

polypeptide is performed using an assay selected from the group consisting of;

(a) ELISA;

(b) radioimmunoassay;

(c) in situ immunoassay;

(d) Western blot;

(e) agglutination assay; and

(f) precipitation reactions.

11. The method of claim 8, wherein the expression level of the soluble Neutrokine-α

polypeptide in serum is greater than 2.0 ng/ml.

12. The method of claim 8, wherein the expression level of the soluble Neutrokine-α

polypeptide in serum is greater than 2.5 ng/ml.

13. The method of claim 8, wherein the expression level of the soluble Neutrokine-α

polypeptide in serum is greater than 3.0 ng/ml.