Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Patent
1995-08-14
1999-09-21
Gardner-Lane, Sally
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
424463, 424520, A61K 948, A61F 1300
Patent
active
059550953
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention is directed to macrocapsules and their use as implantation and retrieval devices for cells.
The methods of implanting living cells and or tissue into the body to provide therapeutically useful substances (cell therapy) is currently the focus of a number of research efforts. Among others, therapeutic applications for cell therapy have been suggested in the areas of diabetes and neural degenerative diseases such as Alzheimer's Disease, Parkinson's Disease and epilepsy. Additionally, cells have also been shown to have great therapeutic potential for the removal of detrimental substances from the body. For example, hepatocytes have been implanted for the treatment of high cholesterol levels as shown by Wang et al., Transplantation Proceedings, 23:894-895 (1991).
In one form of cell therapy, the cells that are implanted into the patient have been genetically modified (transduced) in vitro with exogenous genetic material so as to enable the cells to produce a desired biological substance that is useful as a therapeutic agent. There are variety of mechanisms for transducing cells. Retroviral vectors have been of interest due to the ability of some vectors to transduce a very high percentage of target cells. Replication of target cells is necessary for proviral integration to occur using these vectors. In theory, cells transduced with retroviruses are not able to spread virus to other cells. However, several safety issues surround the use of these systems. Risks include the potential during production of the retroviral vector preparations for contamination with infectious viruses or pathogens (Cornetta, Human Gene Therapy Vol 2:5-14, 1991).
Adenoviruses are also used as gene transfer vectors. They are double stranded DNA viruses capable of infecting post-mitotic cells, and their successful transfection of host cells can result in the expression of large amounts of gene product. Adenoviruses are a minor pathogen in humans and are not normally associated with malignancies. While the adenovirus vector generally remains episomal and does not undergo replication, studies have shown that gene expression can persist for a significant period, opening up the possibility that the vectors are at least replication-competent.
While present cell therapy methods show great therapeutic potential, they have several limitations. The injection of cells into a patient can create a severe immune reaction. An immune reaction to a first injection of cells will most likely preclude a second injection, thus limiting the benefit which can be gained from such treatment. Some candidate cell types may shed virus particles which could be detrimental to the host and therefore may not be considered suitable for implantation. In the case of cells that have been genetically modified to produce a desired biological substance using viral techniques, the cells may harbor viral particles, thus allowing the possibility of infecting a patient's cells. Another disadvantage with the current cell therapy methods is that many cells that might be suitable for such therapies are known to migrate in situ, (e.g. glial cells). The inability to retain implanted cells in a fixed location may make them unsuitable as therapeutic agents. Likewise, cells which are autologous or even allogeneic to the host may continue to divide unchecked and produce tumors.
Current methods of cell therapy do not readily allow termination of, or adjustments to, the cell therapy protocol once the cells are implanted. This is because cells implanted into a patient's body are not well isolated from the patient's own tissue and thus cannot be readily retrieved or manipulated. This creates a real fear when the cells have been genetically modified using retroviral particles because implanted cells could migrate in situ and potentially result in proviral integration into the host germ line cells, thus passing the provirus onto offspring.
There are a number of specific circumstances where it may be critical to terminate or remove implanted the
REFERENCES:
patent: 4353888 (1982-10-01), Sefton
patent: 4803168 (1989-02-01), Jarvis, Jr.
patent: 4806355 (1989-02-01), Goosen et al.
patent: 5015476 (1991-05-01), Cochrum et al.
patent: 5106627 (1992-04-01), Aebischer et al.
patent: 5182111 (1993-01-01), Aebischer et al.
Stanier, et al., "The Bacterial Virus" General Microbiology 373-374 (1976).
Freshney, "Virus Preparation and Assay" Culture of Animal Cells: A Manual of Basic Technique (A John Wiley & Sons, Inc.: New York) pp. 402-403.
Doherty Edward J.
Flanagan Thomas
Gentile Frank T.
Hazlett Tyrone
Holland Laura M.
Brown University Research Foundation
Elrifi Ivor R.
Gardner-Lane Sally
Yankwich Leon R.
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