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

A phase I/II clinical trial has been performed in 12 amyotrophic lateral sc lerosis (ALS) patients to evaluate the safety and tolerability of intrathec al 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 a gainst the implanted xenogeneic cells. Hundreds of pg CNTF/ml could be dete cted for several weeks in the cerebrospinal fluid (CSF) of 9 out of 12 pati ents, in 2 patients up to 20 weeks after capsule implantation. Slightly ele vated leukocyte counts were observed in 6 patients. Clear evidence for a de layed humoral immune response was found in the CSF of only 3 patients out o f 12 (patients #4, #6, and #10). Characterization of the antigen(s) recogni zed by the antibodies present in these CSF samples allowed to identify bovi ne fetuin as the main antigenic component. The defined medium used for main taining the capsules in vitro before implantation contains bovine fetuin. F etuin may therefore still be adsorbed to the surface of the cells and/or th e polymer membrane, or be present in the medium surrounding the encapsulate d cells at the time of implantation. Because of the insufficient availabili ty of CSF samples, as well as the relatively poor sensitivity of the assays used, a weak humoral immune response against components of the implanted c ells 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 n or the presence of antibodies against bovine fetuin elicit any adverse side effects in the implanted patients.