Evaluation of an intrathecal immune response in amyotrophic lateral sclerosis patients implanted with encapsulated genetically engineered xenogeneic cells

Details

Serval ID
serval:BIB_0E4E24BEDE0A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evaluation of an intrathecal immune response in amyotrophic lateral sclerosis patients implanted with encapsulated genetically engineered xenogeneic cells
Journal
Cell Transplantation
Author(s)
Zurn  A. D., Henry  H., Schluep  M., Aubert  V., Winkel  L., Eilers  B., Bachmann  C., Aebischer  P.
ISSN
0963-6897 (Print)
Publication state
Published
Issued date
08/2000
Volume
9
Number
4
Pages
471-84
Notes
Clinical Trial
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul-Aug
Abstract
A phase I/II clinical trial has been performed in 12 amyotrophic lateral sclerosis (ALS) patients to evaluate the safety and tolerability of intrathecal implants of encapsulated genetically engineered baby hamster kidney (BHK) cells releasing human ciliary neurotrophic factor (CNTF). These patients have been assessed for a possible intrathecal or systemic immune response against the implanted xenogeneic cells. Hundreds of pg CNTF/ml could be detected for several weeks in the cerebrospinal fluid (CSF) of 9 out of 12 patients, in 2 patients up to 20 weeks after capsule implantation. Slightly elevated leukocyte counts were observed in 6 patients. Clear evidence for a delayed humoral immune response was found in the CSF of only 3 patients out of 12 (patients #4, #6, and #10). Characterization of the antigen(s) recognized by the antibodies present in these CSF samples allowed to identify bovine fetuin as the main antigenic component. The defined medium used for maintaining the capsules in vitro before implantation contains bovine fetuin. Fetuin may therefore still be adsorbed to the surface of the cells and/or the polymer membrane, or be present in the medium surrounding the encapsulated cells at the time of implantation. Because of the insufficient availability of CSF samples, as well as the relatively poor sensitivity of the assays used, a weak humoral immune response against components of the implanted cells themselves cannot be excluded. However, the present study demonstrates that encapsulated xenogeneic cells implanted intrathecally can survive for up to 20 weeks in the absence of immunosuppression and that neither CNTF nor the presence of antibodies against bovine fetuin elicit any adverse side effects in the implanted patients.
Keywords
Adult Aged Amino Acid Sequence Amyotrophic Lateral Sclerosis/*immunology/therapy Animals Cattle Cell Line *Cell Transplantation Ciliary Neurotrophic Factor/blood/cerebrospinal fluid/*genetics Cricetinae Electrophoresis, Gel, Two-Dimensional Female *Gene Therapy Humans Immunoblotting Male Middle Aged Molecular Sequence Data Transfection *Transplantation Immunology *Transplantation, Heterologous alpha-Fetoproteins/cerebrospinal fluid/chemistry/immunology
Pubmed
Web of science
Create date
25/01/2008 13:46
Last modification date
20/08/2019 13:35
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