The COSTIM bioassay: a novel potency test for dendritic cells.

The utility of dendritic cells (DCs) in experimental immunotherapy has driven significant advances in the manufacture of these cells. They are increasingly prepared in vitro for use in clinical trials of human disease, particularly cancer. Thus, it has become imperative that, in concert with other quality control measures, a potency test be employed for lot (batch)-release testing of DC products, both in preclinical studies and human clinical trials. The mixed lymphocyte reaction (MLR) assay has served as a 'gold standard' for evaluating the functional ability of antigen presenting cells. Alternatively, some researchers also employ immunophenotyping, a test unrelated to cellular function, as a potency-determining test. We have developed a novel method named the 'COSTIM bioassay', which, as we describe in this paper, is suitable for quality control or lot-release testing. In this method T-cells are stimulated with a sub-optimal amount of anti-CD3 antibody, such that they remain unable to proliferate unless a source of co-stimulation (accessory cells, such as DC) is added to the culture. Thus, the COSTIM bioassay is a functional test that selectively measures co-stimulatory activity, or functional potency. This method takes less than 2 days for completion and assures better quality control than the MLR.