Title:  ARPE-19 as a platform cell line for encapsulated cell-based delivery

United States Patent:  6,361,771

Assignee:  Neurotech S.A. (Evry, FR)

Filed:  April 5, 2000

ARPE-19 cells were evaluated as a platform cell line for encapsulated and un-encapsulated cell-based delivery technology. ARPE-19 cells were found to be hardy (the cell line is viable under stringent conditions, such as in central nervous system or intra-ocular environment); can be genetically modified to secrete the protein of choice; has a long life span; is of human origin; has good in vivo device viability; delivers efficacious quantity of growth factor; triggers no or low level host immune reaction, and is non-tumorigenic.

SUMMARY OF THE INVENTION

The ARPE-19 cell line is a superior platform cell line for encapsulated cell based delivery technology and is also useful for unencapsulated cell based delivery technology. The ARPE-19 cell line is hardy (i.e., the cell line is viable under stringent conditions, such as implantation in the central nervous system or the intra-ocular environment). ARPE-19 cells can be genetically modified to secrete a substance of therapeutic interest. ARPE-19 cells have a relatively long life span. ARPE-19 cells are of human origin. Furthermore, encapsulated ARPE-19 cells have good in vivo device viability. ARPE-19 cells can deliver an efficacious quantity of growth factor. ARPE-19 cells elicit a negligible host immune reaction. Moreover, ARPE-19 cells are non-tumorigenic.

The therapeutic usefulness of polymer-encapsulated ARPE-19 cell-based delivery of ciliary neurotrophic factor (CNTF) for treatment of degenerative diseases was shown in both a rodent and canine model of retinitis pigmentosa. ARPE-19 cells were genetically modified to secrete CNTF. Encapsulated genetically modified ARPE-19 cells delivered a consistent amount of CNTF, for example, over a 7-week implantation interval. Cell viability within the encapsulated devices was excellent. The presence of the encapsulated cell device in the eye caused no significant adverse effects on the retina. These results provide a proof of principle for the therapeutic potential of encapsulated ARPE-19 cell-based delivery of desired neurotrophic factors.

Claim 1 of 14 Claims

We claim:

1. An implantable cell culture device, the device comprising:

(a) a semipermeable membrane permitting the diffusion of a growth factor therethrough; and

(b) ARPE-19 cells that are genetically engineered to produce the growth factor disposed within the semipermeable membrane.

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