Genetic induction of receptors for targeted radiotherapy

• US 5,902,583 A
• Filed: 02/11/1997
• Issued: 05/11/1999
• Est. Priority Date: 10/31/1995
• Status: Expired due to Fees

• Current Assignee: UAB Research Foundation (University of Alabama System)
• Original Assignee: UAB Research Foundation (University of Alabama System)
• Inventors: Raben, David, Khazaell, Mohammad B., Buchsbaum, Donald J., Curiel, David T., Stackhouse, Murray
• Primary Examiner(s): Feisee, Lila
• Assistant Examiner(s): SUN HOFFMAN, LIN
• Application Number:
  US08/739,826
• Time in Patent Office: 819 Days
• Field of Search: 435/7, 435/7.2, 435/7.23, 424/85.1, 424/130.1, 424/1.41, 424/1.49, 424/1.65, 424/1.17, 514/44
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/105 Bombesin; Related peptides
• CPC Class Codes: A61K 38/1796 for hormones for neuromediators A61K38/1787
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61K 51/10 Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
• CPC Class Codes: A61K 51/1036 against hormone receptors
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C07K 16/3007 Carcino-embryonic Antigens
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

The present invention provides a method to achieve radioisotopic localization at tumor sites, i.e., a method of enhancing radiolabeled ligand localization to a tumor in an individual in need of such treatment, comprising the steps of: transducing the tumor with a gene encoding a membrane expressed protein unique to the tumor; and administering to said individual a radiolabeled ligand which specifically binds to the protein. The use of gene therapy technology to induce expression of high affinity membrane molecules/receptors can enhance the specificity of radioisotope localization while the use of radioactive isotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency.

Claims

1. An immunodiagnostic method of enhancing radiolabeled ligand localization to a solid tumor in vivo in an individual in need of such diagnosis, comprising the steps of:

transducing said tumor in vivo with a gene encoding a membrane expressed protein unique to said tumor; and

administering to said individual a radiolabeled ligand which specifically binds to said protein.

2. The method of claim 1, wherein said tumor is selected from the group consisting of colon tumors, lung tumors and glioma tumors.

3. The method of claim 2, wherein said tumor is transduced by direct intratumor gene transfer in vivo.

4. The method of claim 1, wherein said tumor is selected from the group consisting of intraperitoneal ovarian tumors and colon tumors.

5. The method of claim 4, wherein said tumor is transduced by intraperitoneal gene transfer in vivo.

6. The method of claim 1, wherein said tumor is an intracerebral glioma tumor.

7. The method of claim 6, wherein said tumor is transduced by stereotactic direct gene transfer.

8. The method of claim 1, wherein said tumor is selected from the group consisting of systemic colon tumors and lung tumors.

9. The method of claim 8, wherein said tumor is transduced by systemic gene transfer.

10. The method of claim 1, wherein said protein is selected from the group consisting of an antigen and a receptor.

11. The method of claim 10, wherein said antigen is epidermal growth factor receptor and the radiolabeled ligand which specifically binds to said antigen is selected from the group consisting of monclonal antibody 528 and monocolonal antibody EGFR1.

12. The method of claim 10, wherein said antigen is the estrogen receptor and the radiolabeled ligand which specifically binds to said antigen is anti-estriol-3-sulfate.

13. The method of claim 10, wherein said receptor is the epidermal growth factor receptor and said radiolabeled ligand is selected from the group consisting of epidermal growth factor and transforming growth factor-alpha.

14. The method of claim 10, wherein said receptor is the estrogen receptor and the radiolabeled ligand which specifically binds to said receptor is selected from the group consisting of tamoxifen, estradiol, estradiol derivatives, estrogen and fluoroalanine.

15. The method of claim 10, wherein said receptor is the gastrin releasing peptide receptor and the radiolabeled ligand which specifically binds to said receptor is selected from the group consisting of bombesin, bombesin analogues and gastrin releasing peptide.

16. The method of claim 10, wherein said receptor is the interleukin-4 receptor and the radiolabeled ligand which specifically binds to said receptor is interleukin-4.

17. The method of claim 10, wherein said receptor is the somatostatin receptor and the radiolabeled ligand which specifically binds to said receptor is octreotide.

18. The method of claim 10, wherein said receptor is the vasoactive intestinal peptide receptor and the radiolabeled ligand which specifically binds to said receptor is vasoactive intestinal peptide.

19. The method of claim 1, wherein said radiolabeled ligand is an antibody.

20. The method of claim 1, wherein said radiolabeled ligand is a peptide.

21. The method of claim 1, wherein said transducion is by adenoviral mediated gene transfer.

22. The method of claim 1, wherein said radiolabel is selected from the group consisting of ¹²³ I, ¹²⁵ I, ¹³¹ I, ³² P, ⁶⁴ Cu, ⁶⁷ Cu, ²¹¹ At, ¹⁷⁷ Lu, ⁹⁰ Y, ¹⁸⁶ Re, ²¹² Pb, ²¹² Bi, ⁴⁷ Sc, ¹⁰⁵ Rh, ¹⁰⁹ Pd, ¹⁵³ Sm, ¹⁸⁸ Re, ¹⁹⁹ Au, ²¹¹ At, and ²¹³ Bi.