Novel method for selection of primate tumor-associated antigens suitable as in vivo targets for antibodies

• US 4,978,520 A
• Filed: 01/11/1989
• Issued: 12/18/1990
• Est. Priority Date: 09/11/1986
• Status: Expired due to Fees

• Current Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• 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:
  US07/295,775
• Time in Patent Office: 706 Days
• Field of Search: 424/85.8, 424/85.91, 424/1.1, 424/9, 436/543, 436/547, 436/548, 530/412, 530/413
• US Class Current: 530/388.8
• 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 39/0005 Vertebrate antigens from snakes A61K39/38
• 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 human 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 other primates, 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 a tumor in vivo in which antibodies are first prepared distinguishable from those present in the animal in which biofiltration is to occur and that bind to antigens present in the tumor to be targeted. These antibodies are then injected into a non-tumor-bearing primate, into a tumor-bearing animal, and into a non-tumor bearing animal of the same species as the tumor-bearing animal to permit biofiltration of the antibodies. The biofiltered antibodies are next recovered from each of the non-tumor-bearing primate, the tumor-bearing animal, and the non-tumor-bearing animal and are employed to identify antigens whose antibodies are not retained in vivo in the primate and the non-tumor-bearing animal. The antibodies that are not retained in vivo by the non-tumor-bearing primate and the non-tumor bearing animal are then compared with those antibodies that are actually retained in vivo in the tumor-bearing animal to identify the antigens corresponding to those antibodies that are selectively retained in the tumor-bearing animal.

Claims

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

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

(b) injecting the prepared antibodies into a non-tumor-bearing primate, into a tumor-bearing animal, and into a non-tumor bearing animal of the same species as the tumor-bearing animal said primate being of a species other than the tumor-bearing or the non-tumor-bearing animal;

(c) recovering the biofiltered antibodies from each of the non-tumor-bearing primate and the tumor-bearing animal and the non-tumor-bearing animal;

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

(e) comparing the antibodies that are not retained in vivo by the non-tumor-bearing primate and the non-tumor-bearing animal with those antibodies that are actually retained in vivo in the tumor-bearing animal to identify the antigens corresponding to those antibodies that are selectively 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), radiolabeling the selected antibodies and injecting the radiolabeled 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 primate and 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 primate and 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.