Modulation of systemic cytokine levels by implantation of alginate encapsulated cells

Abstract

The availability of cell lines that are transfected with IL-4, IL-5 and IFN-gamma cytokine genes permits the prolonged in vivo delivery of functional cytokines in relatively large doses for the modulation of specific immune responses. Often the transfected cells are xenogeneic or allogeneic to the experimental animal and have to be encapsulated in such a way that no cellular response by the host will be induced. Alginate has proven to be a simple matrix for encapsulating cells under mild conditions suitable for in vivo implantation. Encapsulated cells express the transfected IL-4 gene for at least 14 days after in vivo implantation and were shown to be functional during that period by modulating ongoing IgE responses. The application of adherent growing transfected cells permits dose-response titrations and provides an easy method for local and systemic cytokine delivery. Alternatively, hybridoma cells can be encapsulated and the secreted antibody monitored in the serum. It was found that no host immune response was triggered by alginate encapsulated cells. The efficiency of treatment by encapsulated hybridoma cells was shown to be equivalent to that of injecting purified antibodies.

Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells

“…Rat hybridoma cells secreting a mAb directed against murine IL-4 have been encapsulated in alginate and implanted intraperitoneally and subcutaneously into mice. 9 Serum antibody concentrations were comparable with those reached in our experiments. However, the levels of antibody delivered in the blood stream declined after 14 days as a consequence of capsule deterioration.…”

“…Second, they must be small enough to prevent, on one hand, the encapsulated cells from leaving the capsules and, on the other hand, cells of the host immune system from entering the capsules. Several types of polymers, such as alginate, 9 alginate-poly(l)lysine-alginate, 8,10 various acrylic polymers 11,12 and cellulose sulphate 13 have already been used for encapsulating cells. The various matrices differ in their physical and mechanical properties.…”

Immunotherapy with monoclonal antibodies directed against the immunosuppressive domain of p15E inhibits tumour growth

“…Technical aspects of hybridoma encapsulation for immunotherapy Encapsulation of hybridomas in alginate was performed according to the method described by Savelkoul et al and Hashimoto & Shirai [16,18]. Encapsulated hybridoma cells produced MoAbs in vitro as expected: supernatant derived from cultures of encapsulated hybridoma cells showed the same reactivity for RMB-1 cells as did supernatant from hybridoma tissue cultures.…”

Suppression of polyclonal and antigen‐specific murine IgG1 but not IgE responses by neutralizing interleukin‐6 in vivo

“…Alternatively, mice were implanted with 2 x lo6 alginate-encapsulated 11B11 and/or 20F3 hybridoma cells i.p. [20]. The hybridoma cells encapsulated in alginate were implanted in mice 3 days before immunization, the purified antibodies were given 2 h before immunization.…”

“…The hybridoma cells encapsulated in alginate were implanted in mice 3 days before immunization, the purified antibodies were given 2 h before immunization. The rat IgGl production by these l l B l l and/or 20F3 cells was determined in the serum using a rat IgG1-specific ELISA as described previously [20]. Purified rat mAb specific for E. coli P-galactosidase (GL113) [21] or 2 x lo6 alginate-encapsulated GL113 cells were used as an IgGl isotype control.…”