Method for selection of antigens suitable as in vivo targets for antibodies

• US 4,798,719 A
• Filed: 09/11/1986
• Issued: 01/17/1989
• Est. Priority Date: 09/11/1986
• Status: Expired due to Term

• Current Assignee: University of Pittsburgh Cathedral of Learning A Non-Profit Corporation of PA
• Original Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Inventors: Ballou, Byron T.
• Primary Examiner(s): Maples, John S.
• Application Number:
  US06/906,161
• Time in Patent Office: 859 Days
• Field of Search: 424/1.1, 424/9, 436/543, 436/547, 436/548, 530/412, 530/413
• US Class Current: 424/1.49
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 51/106 the tumor cell being from kidney or bladder
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57438 of liver, pancreas or kidney
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92

Abstract

The present invention is a process for the selection of antigens which are suitable targets for in vivo antibody localization in tumors or other altered (or diseased) tissue. The process provides a simplified and rapid technique for discovering useful in vivo targets for antibodies and is useful in cancer detection and therapy in humans or animals, whether or not the antigens are specific to tumors.

More specifically, the invention relates to a process for the selection of antigens suitable as targets for antibodies which localize in tumors in animals in vivo comprising preparing antibodies distinguishable from those present in the animal in which tumor targeting is to occur and that bind to antigens present in the tumor in said animal; injecting the prepared antibodies into a non-tumor-bearing animal to permit biofiltration of the antibodies; recovering the biofiltered antibodies from the non-tumor-bearing animal; employing the recovered biofiltered antibodies to identify antigens whose antibodies are not retained in vivo in the animal; and screening the antibodies that are not retained in vivo by the non-tumor bearing animal both to determine those antibodies that are actually retained in vivo in the tumor-bearing animal and to identify the antigens corresponding to those antibodies retained in the tumor-bearing animal.

Claims

1. A process for the selection of antigens suitable as targets for antibodies which localize in tumors in animals in vivo comprising:

(a) preparing antibodies distinguishable from those present in the animal in which tumor targeting is to occur and that bind to antigens present in the tumor in said animal;

(b) injecting the prepared antibodies into a non-tumor-bearing animal and into a tumor-bearing animal to permit biofiltration of the antibodies;

(c) recovering the biofiltered antibodies from both the non-tumor-bearing animal and the tumor-bearing animal;

(d) identifying antigens whose antibodies are not retained in vivo in the non-tumor-bearing animal, but are retained in vivo in the tumor-bearing animal using the recovered biofiltered antibodies; and

(e) screening the antibodies that are not retained in vivo by the non-tumor-bearing animal and the antibodies that are not retained in vivo by the tumor-bearing animal to determine those antibodies that are actually retained in vivo in the tumor-bearing animal and to identify the antigens corresponding to those antibodies retained in the tumor-bearing animal.

2. The process of claim 1 wherein the screening in step (e) further comprises selecting specific antibodies which survive the biopurification of step (b), radiolabelling the selected antibodies and injecting the radiolabelled selected antibodies into the tumor-bearing animal.

3. The process of claim 1 further comprising:

(f) preparing monoclonal antibodies using the antigens identified in step (e) as immunogens.

4. The process of claim 1 wherein the antibodies prepared in step (a) are xenoantibodies.

5. The process of claim 4 wherein the antibodies prepared in step (a) are polyclonal xenoantibodies.

6. The process of claim 1 wherein antigens whose antibodies are not retained in vivo in the non-tumor-bearing animal are identified in step (d) by a biochemical method.

7. The process of claim 6 wherein antigens whose antibodies are not retained in vivo in the non-tumor-bearing animal are identified in step (d) using a biochemical method selected from the group consisting of Western blots, immunoprecipitation and solid-phase adsorption.