Method of evaluating chemotherapeutic agents in vivo

• US 5,698,413 A
• Filed: 05/05/1993
• Issued: 12/16/1997
• Est. Priority Date: 05/05/1993
• Status: Expired due to Term

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Hollingshead, Melinda G.
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): Mohamed, Abdel A.
• Application Number:
  US08/058,154
• Time in Patent Office: 1,686 Days
• Field of Search: 435/32, 435/182, 435/240.1, 435/240.22, 435/240.242, 424/422, 424/423, 424/424, 264/4, 264/4.7
• US Class Current: 435/32
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 49/0008 Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
• CPC Class Codes: C12N 2503/02 Drug screening
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0693 Tumour cells; Cancer cells
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics

Abstract

The present invention relates to a method of screening chemotherapeutic agents in vivo. The method comprises implanting into a laboratory animal a biocompatible, semi-permeable encapsulation device containing a target cell-line, treating the laboratory animal with a test agent, then evaluating the target cells for reaction to the test agent.

Claims

1. A method of screening chemotherapeutic agents in vivo comprising the steps of:

(a) implanting into a mammal at least one biocompatible, tubular, semi-permeable encapsulation device containing a group of target cells within an interior of said device wherein said device has a molecular weight cut off of greater than 50,000 daltons and said device is comprised of polyvinylidine fluoride;

(b) treating said mammal with at least one chemotherapeutic agent; and

(c) evaluating said target cells for reaction to the at least one chemotherapeutic agent.

4. The method of claim 1, 2, or 3, wherein said biocompatible, semi-permeable tubular encapsulation device has a molecular weight cutoff of less than about 500,000 daltons.

5. The method of claims 1, 2, or 3, wherein a multiplicity of encapsulation devices is implanted.

6. The method of claims 1, 2, or 3, wherein said implanting step comprises subcutaneous, intraperitoneal, or intraorgan implantation.

7. The method of claims 1, 2, or 3, wherein at least one encapsulation device is implanted subcutaneously and at least one encapsulation device is implanted intraperitoneally.

8. The method of claims 1, 2, or 3, wherein said encapsulation devices are each instilled with the same target cells.

9. The method of claims 1, 2, or 3, wherein said encapsulation devices are each instilled with different target cells.

10. The method of claims 1, 2, or 3 wherein said target cells are selected from the group consisting of tumor cells, fibroblasts, leukocytes, lymphoid cells, cultured primary cells, bacteria, virus-infected cells, yeast and fungi.

11. The method of claim 1, 2, or 3, wherein said target cells are selected from the group consisting of melanomas, lung tumor lines, prostate tumor lines, ovarian tumor lines, breast tumor lines, renal tumor lines, colon tumor lines, central nervous system tumor lines, leukemic or lymphoma cell lines, tumor xenografts and fresh patient derived tumor tissue.

12. The method of claim 1, 2, or 3, wherein said target cells are infected with a virus incapable of replication in said mammal.

13. The method of claims 1, 2, or 3, wherein said mammal is selected from the group consisting of mouse, rat, hamster, guinea pig, rabbit, cat, and dog.

2. A method of screening chemotherapeutic agents in vivo, comprising the steps of:

(a) implanting into a mammal at least one biocompatible, tubular, semi-permeable encapsulation device containing a group of target cells within an interior of said device, wherein said device has a molecular weight cutoff of greater than 100,000 daltons;

(b) treating said mammal with at least one chemotherapeutic agent; and

(c) evaluating said target cells for reaction to the at least one chemotherapeutic agent.

3. A method of screening chemotherapeutic agents, in vivo comprising the steps of:

(a) implanting into a mammal at least one biocompatible, tubular, semi-permeable encapsulation device, containing a group of target cells within an interior of said device, said device being comprised of polyvinylidene fluoride;

(b) treating said mammal with at least one chemotherapeutic agent; and

(c) evaluating said target cells for said reaction to the at least one chemotherapeutic agent.

14. A method of screening chemotherapeutic agents in vivo comprising the steps of:

(a) implanting into a mammal at least one biocompatible, tubular, semi-permeable encapsulation device containing a group of target cells infected with a virus;

(b) treating said mammal with at least one chemotherapeutic agent; and

(c) evaluating said vital infection in said target cells for effect by the at least one chemotherapeutic agent.

15. The method of claim 14, wherein said biocompatible, semi-permeable encapsulation device has a molecular weight cutoff of between about 50,000 daltons and about 500,000 daltons.

16. The method of claims 14, wherein a multiplicity of encapsulation devices is implanted.

17. The method of claim 14, wherein at least one encapsulation device is implanted subcutaneously and at least one encapsulation device is implanted intraperitoneally.

18. The method of claim 14 wherein said implanting step comprises subcutaneous, intraperitoneal, or intraorgan implantation.

19. The method of claim 14 wherein said encapsulation devices are each instilled with the same target cell.

20. The method of claims 14 wherein said encapsulation devices are each instilled with different target cells.

21. The method of claim 14 wherein said target cells are selected from the group consisting of tumor cells, fibroblasts, leukocytes, lymphoid cells, cultured primary cells, bacteria, yeast, and fungi.

22. The method of claim 14 wherein said target cells are selected from the group consisting of said tumor cells are selected from the group consisting of melanomas, lung tumor lines, prostate tumor lines, ovarian tumor lines, breast tumor lines, renal tumor lines, colon tumor lines, central nervous system tumor lines, leukemic or lymphoma cell lines, tumor xenografts and fresh patient derived tumor tissue.

23. The method of claim 14 wherein said mammal is selected from the group consisting of mouse, rat, hamster, guinea pig, rabbit, cat and dog.

24. The method of claim 14 wherein said target cell is infected with a virus incapable of replication in said mammal.

25. The method of claim 14 wherein said device is comprised of a material selected from the group consisting of polysulfone, polyvinylidene fluoride, cellulose acetate, saponified cellulose ester, polypropylene, polyamide, polyvinyl chloride, and acrylic co-polymer.

26. The method of claim 25 wherein said device is comprised of polyvinylidene fluoride.

27. The method of claim 14 wherein said target cell is a retrovirus infected cell.

28. The method of claim 27 wherein said retrovirus-infected cell comprises the human immunodeficiency virus.