Methods and reagents for improved treatment and diagnostic imaging, particularly of cancer. The methods and reagents utilize specific targeting of treatment and imaging ligands (TL) to the targeted tumor, or specific organ or tissue, in association with extracorporeal affinity adsorption of the targeted ligand. The targeted species include antibodies as well as other peptides with specific affinity to the targeted tumor organ or tissue. Included are hybrid targeting moledules (TAB), such as hybrid F(ab')2, with one binding site (BP1) specific for the target and the other binding site (BP2) specific for the targeted treatment or visualization ligand. The affinity adsorption devices may include adsorbents (EB) specific to one or more of the components of the targeting molecule-targeted ligand moiety. The methods and reagents provide for improved treatment, particularly in cancer and HIV, by increasing the concentration in the tumor and decreasing the concentration in the rest of the body, thus reducing its toxicity and enabling the use of high doses of drugs and other treatment agents. Improved visualization of cancer is provided by increased concentration of visualization ligand in the cancer and reduced concentration in the blood and normal tissues.

Claims

I claim:

1. A method of attaching an antibody to a site in an organism, the method comprising a step of preparing a hybrid antibody having a first portion specific to the site and a second portion specific to a second antigen or hapten, a step of introducing the antibody into the organism to bind with the site, a step of binding the second antigen or hapten to the second portion of the hybrid antibody, and a removal step, after the step of introducing the antibody, of removing by affinity adsorption at least one of the group consisting of the hybrid antibody, the hybrid antibody bound to the second antigen or hapten, and the second antigen or hapten.

2. The method of claim 1 wherein the step of binding the second antigen or hapten to the second portion of the hybrid antibody is carried out before the step of introducing the antibody into the organism.

3. The method of claim 1 wherein the second antigen or hapten includes a tracer for visualization of the site in the organism.

4. The method of claim 3 wherein the tracer is radioactive.

5. The method of claim 1 wherein the second antigen or hapten is a treatment ligand.

6. The method of claim 5 wherein the treatment ligand is chosen from the group consisting of a drug, a radioactive isotope, and a biological toxin.

7. The method of claim 1 wherein the removal step comprises immunoadsorption of the hybrid antibody.

8. The method of claim 7 wherein the immunoadsorption step includes binding of the hybrid antibody to an immunoadsorbent chosen from the group consisting of protein A and protein G.

9. The method of claim 7 wherein the removal step comprises a step of binding at least one of the first portion and the second portion of the hybrid antibody to an antigen.

10. The method of claim 1 wherein the removal step comprises immunoadsorption of the second antigen or hapten.

11. The method of claim 1 wherein the removal step comprises immunoadsorption in a chamber of a device external to the organism.

12. The method of claim 11 wherein the removal step comprises immunoadsorption with an immunoadsorbent chosen from the group consisting of staphylococcal protein A and protein G.

13. The method of claim 11 wherein the organism is a mammal and wherein the device is an extracorporeal device connected to the mammal.

14. The method of claim 13 wherein the extracorporeal device is connected in the blood circulatory system of the mammal.

15. The method of claim 13 wherein the removal step comprises a step of binding at least one of the first portion and the second portion of the hybrid antibody to an antigen bound in the extracorporeal device.

16. The method of claim 13 wherein the removal step comprises immunoadsorption of the antigen or hapten by an antibody bound in the extracorporeal device.

17. A method of producing a liposome attached to an antibody comprising a step of covalently binding an antigen to the surface of the liposome, and thereafter a step of binding the antibody to the antigen.

18. The method of claim 17 wherein the antibody is a hybrid antibody having a first portion specific to the antigen bound to the liposome and a second portion specific to a second antigen.

19. The method of claim 18 wherein the second portion of the hybrid antibody is specific to a site in an organism.

20. A method of attaching a liposome to a site in an organism, the method comprising a step of binding to the surface of the liposome a species targeting the site, thereafter a step of introducing the liposome into the organism to bind with the site, and thereafter a step of removing the liposome by affinity binding.

21. The method of claim 20 wherein the step of removing the liposome is by immunologic binding of the species bound to the surface of the liposome.

22. The method of claim 20 wherein the species is an antibody.

23. A method of delivering a ligand to a site in an organism, the method comprising a step of binding to the surface of the liposome a species targeting the site, a step of entrapping free ligand in the liposome, thereafter a step of introducing the liposome into the organism to bind with the site, and thereafter a step of removing by affinity binding at least one of the group consisting of the liposome and the ligand.

24. The method of claim 23 wherein the affinity adsorption is immunoadsorption and the immunoadsorbent is an antibody to the free ligand.

25. The method of claim 23 wherein the targeting species is an enzyme with affinity to the targeting site.

26. The method of claim 23 wherein the targeting species is a drug which has affinity to the targeting site.

27. The method of claim 23 wherein the targeting species is a hormone which has affinity to the targeting site.

28. The method of claim 23 wherein the targeting species is the CD4 molecule of T4 lymphocytes.

29. The method of claim 28 wherein the targeting species is chosen from the group consisting of natural fragment, synthetic fragment, genetically produced fragment, or synthetic analog of the CD4 molecule having affinity to a binding site on the HIV1 virus.

30. The method of claim 23 wherein the targeting species is an antibody or fragment of antibody with affinity to a binding site on the HIV I virus and wherein an anti-HIV1 drug is entrapped in the liposome.

31. A method of delivering an antibody or hapten to a site in an organism, the method comprising a step of trapping in a liposome a hybrid antibody including a first portion specific to the site and a second portion specific to the antigen or hapten, a step of introducing the liposome into the organism, and a step of binding the antigen or hapten to the second portion of the hybrid antibody.

32. The method of claim 31 wherein the step of binding the antigen or hapten to the second portion of the hybrid antibody is carried out before the step of introducing the liposome into the organism.

33. In an immunologic assay method for determining a species in a sample, the method including a step utilizing an immunologically binding tracer, the improvement wherein the tracer comprises a liposome having a detection ligand entrapped therein, the liposome having a wall with an immunologic binding moiety attached to the wall.

34. The improvement of claim 33 wherein the immunologic binding moiety comprises a hapten or antigen covalently bound to the liposome wall.

35. The improvement of claim 33 wherein the detection ligand comprises a radioactive isotope.

36. The improvement of claim 33 wherein the detection ligand comprises a color-producing reagent.

37. The improvement of claim 33 wherein the assay method comprises an inhibition assay.

38. The method of claim 21 wherein the step of removing the liposome comprises immunoadsorption with an immunoadsorbent chosen from the group consisting of staphylococcal protein A and protein G.

39. A liposome containing trapped therein a plurality of hybrid antibodies including a first portion specific to a first antigen or hapten and a second portion specific to a second antigen or hapten.

40. A reagent comprising a liposome, an antigen or hapten covalently bound to a wall of the liposome, and an antibody to the antigen immunologically bound to the antigen or hapten.

41. The reagent of claim 40 wherein the antibody is a hybrid antibody having a first portion specific to the antigen bound to the liposome wall and a second portion specific to a second antigen or hapten.

42. The reagent of claim 41 wherein the second portion of the hybrid antibody is specific to a site in an organism.

43. In combination, the reagent of claim 42 and a second reagent or a device capable of removing the reagent of claim 42 by affinity binding.

44. The combination of claim 45 wherein the second reagent or device is an immunologic affinity binding reagent or device.

45. The combination of claim 44 wherein the affinity binding reagent or device includes an antibody as the affinity adsorption species.

46. In combination, a liposome to which is attached a species targeting a site in an organism, a free ligand entrapped in the liposome, and a second reagent or device, capable of removing from the organism by affinity binding at least one of the group consisting of the liposome and the ligand.

47. The combination of claim 46 wherein the second reagent or device includes an antibody to the free ligand as the affinity binding species.

48. The combination of claim 46 wherein the targeting species is an enzyme with affinity to the targeting site.

49. The combination of claim 46 wherein the targeting species is a drug which has affinity to the targeting site.

50. The combination of claim 46 wherein the targeting species is a hormone which has affinity to the targeting site.

51. The combination of claim 46 wherein.the targeting species is the CD4 molecule of T4 lymphocytes.

52. The method of claim 28 wherein the targeting species is chosen from the group consisting of natural fragment, synthetic fragment, genetically produced fragment, or synthetic analog of the CD4 molecule having affinity to a binding site on the HIV1 virus.

53. The combination of claim 46 wherein the targeting species is an antibody or fragment of antibody with affinity to a binding site on the HIV1 virus and wherein an anti-HIV 1 drug is entrapped in the liposome.

54. In combination, an antigen or hapten and a liposome containing a hybrid antibody entrapped therein, the hybrid antibody including a first portion specific to a site in an organism and a second portion specific to the antigen or hapten.

55. The combination of claim 54 wherein the antigen or hapten and the liposome are contained in a package.

56. The combination of claim 46 wherein the liposome and the second reagent or device are contained in a package.

57. The combination of claim 43 wherein the liposome and the second reagent or device are contained in a package.

58. The combination of claim 44 wherein the immunologic affinity binding reagent or device includes protein A or protein G as the immunologic binding species.

Click Here for Other Patents Available for Licensing