Development of a delivery system for the continuous endogenous release of an anti-idiotypic antibody against ovarian carcinoma.

摘要

The treatment of several cancers with anti-idiotype antibodies has shown promising results in animals and clinical trials. A common drawback of many anti-idiotypic antibodies is their low immunogenicity. The aim of this work was to construct a new delivery form for the anti-idiotypic antibody ACA125hFc, with the goal of improving its immunogenicity as vaccine against ovarian carcinoma. Designed on bioencapsulation technologies, we generated an in vitro depot that acts as a continuous delivery system for the anti-idiotypic antibody ACA125hFc. C2C12 myoblasts were transfected with the anti-idiotypic chimeric antibody ACA125hFc, which mimics the CA125 tumor antigen and which consists of variable regions of the monoclonal murine antibody ACA125 (currently in clinical trial) and the human IgG Fc domain. Recombinant myoblasts were encapsulated in 1-cm semipermeable, polyethersulfone (PES), or polyvinylidene difluoride (PVDF) hollow fibers, which differ in their molecular weight cutoff (MWCO). Encapsulated cells were evaluated in vitro for viability and antibody secretion over a period of 3 months. PES hollow fibers with a higher MWCO showed a twofold higher secretion rate of chACA125hFc compared to PES devices with a lower MWCO. No remarkable level of ACA125hFc could be detected for PVDF devices. The expression levels of the anti-idiotypic antibody ACA125hFc from capsules with a lower MWCO could be improved substantially, in both PES as well as PVDF, by inserting an internal polyethyleneterephtalate (PET) yarn. We conclude that murine recombinant C2C12 myoblasts encapsulated in PES as well as PVDF hollow fibers containing an internal PET matrix can act as a long-term secretion system for anti-idiotypic antibodies.