DRUG-SPECIFIC PHARMACOKINETIC ASSAY FOR IL-15 SUPERAGONIST

1 . A composition comprising:

i. an interleukin-15 (IL-15)/interleukin-15 receptor alpha Sushi domain (IL-15RαSu) complex comprising:

a) a first IL-15RαSu domain;

b) a second IL-15RαSu domain, wherein the first and second IL-15RαSu domains are directly or indirectly joined by a disulfide bond;

c) a first IL-15 domain, bound by electrostatic interactions to the first IL-15RαSu domain to form a first IL-15/IL-15RαSu complex;

d) a second IL-15 domain, bound by electrostatic interactions to the second IL-15RαSu domain to form a second IL-15/IL-15RαSu complex;

ii. a first monoclonal antibody (mAb) bound to an epitope on the first IL-15/IL-15RαSu complex, wherein the first monoclonal antibody comprises a means for conjugation to a polymeric surface; and

iii. a second mAb bound to the second IL-15/IL-15RαSu complex, wherein the second mAb comprises a detection means selected from the group consisting of a fluorophore, a radioisotope, and an enzyme, and wherein both the first mAb and the second mAb comprise the same epitope binding domain.

2 . The composition of claim 1 , wherein at least one of the IL-15 domains comprises an asparagine-to-aspartate mutation at amino acid position 72 (N72D).

3 . The composition of claim 1 , wherein the IL-15RαSu domains each further comprise an immunoglobulin crystallizable fragment (Fc) domain.

4 . The composition of claim 3 , wherein the means for conjugating the first mAb to the polymeric surface comprises biotinylation.

5 . (canceled)

6 . (canceled)

7 . The composition of claim 3 , wherein the IL-15 domains further comprise a single chain variable fragment (scFv) domain.

8 . The composition of claim 3 , wherein the IL-15RαSu domains further comprise an scFv domain.

9 . A method for detecting a heterotetrameric IL-15/IL-15RαSu complex in a biological sample, the method comprising:

a) contacting the biological sample comprising the IL-15/IL-15RαSu complex with a first mAb, wherein the mAb is conjugated to a polymeric surface, wherein the IL-15/IL-15RαSu complex comprises two IL-15 domains and two IL-15RαSu, wherein each IL-15 domain is electrostatically bound to an IL-15RαSu domain, wherein the two IL-15RαSu domains are directly or indirectly bound to each other by a disulfide bond, and wherein the Fab portion of the mAb binds an epitope on the IL-15/IL-15RαSu complex with an affinity between 500 nM and 1 fM;

b) contacting the biological sample with a second mAb under conditions such that the second antibody binds with the same affinity to the identical epitope on the second IL-15/IL-15RαSu complex, wherein the second mAb comprises a detection means selected from the group consisting of a fluorophore, a radioisotope, and an enzyme;

c) washing unbound complexes from the polymeric surface; and detecting binding of the second mAb.

10 . The method of claim 9 , wherein at least one of the IL-15 domains comprises an N72D mutation.

11 . The method of claim 9 , wherein the IL-15RαSu domains each further comprise an Fc domain.

12 . (canceled)

13 . (canceled)

14 . The method of claim 11 , wherein the polymeric surface is a polypropylene or polystyrene surface.

15 . The method of claim 9 , wherein the first mAb and the second mAb have substantially the same amino acid sequence.

16 . The method of claim 11 , wherein the IL-15 domains each further comprise an scFv domain.

17 . The composition of claim 1 , wherein the first and second IL-15RαSu domains are directly joined by a disulfide bond.

18 . The composition of claim 3 , wherein the first and second IL-15RαSu domains are indirectly joined by a disulfide bond between the Fc domains.

19 . The method of claim 9 , wherein the first and second IL-15RαSu domains are directly joined by a disulfide bond.

20 . The method of claim 11 , wherein the first and second IL-15RαSu domains are indirectly joined by a disulfide bond between the Fc domains.