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.TM., 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.
