Selective removal of immunospecifically recognizable substances from solution

• US 4,551,435 A
• Filed: 08/24/1983
• Issued: 11/05/1985
• Est. Priority Date: 08/24/1983
• Status: Expired due to Fees

• Current Assignee: Immunivest Corporation
• Original Assignee: Immunicon Corporation
• Inventors: Liberti, Paul A., Pollara, Paul
• Primary Examiner(s): Marantz, Sidney
• Application Number:
  US06/526,039
• Time in Patent Office: 804 Days
• Field of Search: 436/512, 436/821, 436/507, 436/509, 436/519, 436/531, 436/541
• US Class Current: 436/541
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: B01D 15/3809 of the antigen-antibody type, e.g. protein A, G, L chromatography
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: Y10S 436/821 involving complement factors or complement systems

Abstract

A process and apparatus for removing immuno-specifically recognizable substances in the form of immune complexes from a solution. The solution containing preformed immune complexes or immune complexes already present therein is contacted with an adsorbent consisting of non-immunospecific factor such as Clq, rheumatoid factor, Fc receptor and Fc receptor-bearing cells.

Claims

1. A method for selectively removing from a solution any soluble or suspended immunospecifically recognizable substance, which method comprises the steps of:

a. determining the amount of said substance present in said solution;

b. adding to said solution an immunospecific component capable of reacting specifically with said substance, said component being added in a quantity appropriate to form immune complexes with the amount of said substance determined to be present in said solution, said immune complexes being capable of binding to non-immunospecific factor having an affinity therefor; and

c. contacting said solution with an adsorbent comprising non-immunospecific factor which exhibits an affinity for said immune complexes, whereby said immune complexes become bound to said non-immunospecific factor and said immunospecifically recognizable substance is substantially completely removed from said solution.

2. A method according to claim 1, wherein said substance to be removed from said solution is an antigen and said immunospecific component added to said solution to form said immune complex is the corresponding antibody specific to said antigen.

3. A method according to claim 1, wherein said substance to be removed from said solution is an antibody and said immunospecific component added to said solution to form said immune complex is the corresponding antigen specific to said antibody.

4. The method according to claim 1, wherein said adding immunospecific component comprises a first constituent which is not capable of forming with said substance an immune complex which can be readily adsorbed by said non-immunospecific factor, and a second constituent which binds to said first constituent, and forms with said first constituent and said substance an immune complex which can be adsorbed by said non-immune specific factor, whereby said added component is removed out of said solution with said substance.

5. The method according to claim 1, wherein said non-immunospecific factor is selected from the group consisting of Clq, rheumatoid factor and Fc receptor or Fc receptor-bearing cells, said Fc receptor or Fc receptor-bearing cells being characterized by a binding affinity for aggregated antibody, and not for monomeric antibody.

6. A method according to claim 1, wherein said non-immunospecific factor is Fc receptor or Fc receptor-bearing cells, said Fc receptor or Fc receptor-bearing cells being characterized by a binding affinity for aggregated antibody, and not for monomeric antibody.

7. A method according to claim 1, wherein said immunospecifically recognizable substance is a cell having antigenic reactive sites associated therewith and said immunospecific component added to said solution to form said immune complexes is antibody which reacts specifically with said antigenic reactive sites.

8. A process according to claim 1, wherein the temperature of the solution is between about 5°

C. and about 10°

C.

9. A method according to claim 1, wherein said adsorbent consists essentially of a solid phase having affixed thereon said non-immunospecific factor, and said contacting step comprises passing said solution containing said immune complex into contact with said solid phase having said non-immunospecific factor affixed thereon.

10. The method according to claim 9, including the additional step of separating said complex from said adsorbent by isolating said adsorbent from said solution and desorbing said immune complex bound to said non-immunospecific factor.

11. The method according to claim 1, wherein said solution is biological fluid.

12. The method according to claim 11, wherein said biological fluid comprises intravascular fluid derived from a host.

13. The method according to claim 12, wherein said intravascular fluid substantially completely free of said immune complex is returned to the intravascular system of said host.

14. The method according to claim 12, wherein said intravascular fluid comprises bone marrow.

15. The method according to claim 12, wherein said intravascular fluid comprises blood.

16. The method according to claim 15, including the additional step of lowering the levels of endogenous factors which react with said immune complexes prior to said step of contacting said solution with said adsorbent.

17. The method according to claim 16, wherein said endogenous factors whose levels are lowered are selected from the group consisting of Clq, rheumatoid factor and Fc receptors or Fc receptor-bearing cells.

18. The method according to claim 15, including the additional step of suppressing coagulation, complement and platelet activation systems prior to said step of contacting said solution with said adsorbent for adsorption of said immune complexes.

19. The method according to claim 18, wherein said systems are suppressed by adding a chelating agent to said intravascular fluid in an amount sufficient to effect the chelation of calcium and magnesium ions present therein.

20. The method according to claim 18, wherein said systems are suppressed by cooling said intravascular fluid to about 5°

C. to about 10°

C.