Delivery of therapeutic biologicals from implantable tissue matrices

• US 6,692,738 B2
• Filed: 01/26/2001
• Issued: 02/17/2004
• Est. Priority Date: 01/27/2000
• Status: Expired due to Fees

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Masiakos, Peter T., MacLaughlin, David T., Vacanti, Joseph P., Donahoe, Patricia K.
• Primary Examiner(s): Shukla, Ram R.
• Application Number:
  US09/770,339
• Publication Number:
  US 20020031500A1
• Time in Patent Office: 1,117 Days
• Field of Search: 424/93.21, 424/486, 424/484, 424/497, 514/44, 435/325, 435/320.1, 435/455
• US Class Current: 424/93.21
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• 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: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 30/00 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 5/0656 Adult fibroblasts

Abstract

Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.

Claims

1. A method for treating abnormal cell or tissue growth that is treatable with MIS, in a subject in need thereof, comprising implanting in the subject a cell-matrix structure, wherein the cell-matrix structure comprises a matrix having attached thereto allogeneic or autologous cells that have been genetically engineered to stably express MIS in an amount sufficient to treat the abnormal cell or tissue growth, and wherein the abnormal cell or tissue growth is vulvar epidermoid carcinoma, cervical carcinoma, endometrial adenocarcinoma, ovarian adenocarcinoma, or a breast tumor.

2. The method of claim 1 wherein the abnormal cell or tissue growth is.

3. The method of claim 1 wherein the matrix is selected from the group consisting of fibrous scaffolds, polymeric hydrogels, and micromachine or micromolded substrates.

4. The method of claim 1 wherein the cells that have been genetically engineered are of a different cell type than the abnormal cell or tissue.

5. The method of claim 1 wherein the abnonnal cell or tissue growth is ovarian adenocarcinoma.

6. The method of claim 1 wherein the abnormal cell or tissue growth is malignant.

7. The method of claim 1 wherein the tissue is ovarian tissue.

8. The method of claim 1 wherein the matrix comprises a biodegradable polymer of polyglycolic acid.