Release characteristics of cellulose sulphate capsules and production of cytokines from encapsulated cells

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The size and speed of release of proteins of different sizes from standard cellulose sulphate capsules (Cell-in-a-Box®) was investigated. Proteins with molecular weights of up to around 70kD can be released. The conformation, charge and concentration of the protein being released play a role in the release kinetics. Small proteins such as cytokines can be easily released. The ability to produce cytokines at a sustained and predefined level from encapsulated cells genetically engineered to overexpress such cytokines and implanted into patients may aid immunotherapies of cancer as well as infectious and other diseases. It will also allow allogeneic rather than autologous cells to be used. We show that cells encapsulated in polymers of cellulose sulphate are able to release cytokines such as interleukin-2 (IL-2) in a stimulated fashion e.g. using phorbol 12-myristate 13-acetate (PMA) plus ionomycin. Given the excellent documented safety record of cellulose sulphate in patients, these data suggest that clinical usage of the technology may be warranted for cancer treatment and other diseases.

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