The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development.

We assessed the potential for an allogeneic-based vaccine against HIV infection in women who were allo-immunized with their partners' mononuclear leucocytes to prevent spontaneous recurrent abortion. Within 1 month of allo-immunization, there was significant upregulation in the concentrations of CD8 cell-derived suppressor factor activity, RANTES, and macrophage inflammatory proteins 1alpha and 1beta. Allo-immunization also downregulated the proportion of cells with CCR5 and CXCR4 receptors. We also found a dose-dependent decrease in HIV infectivity of CD4+ cells in vitro after allo-immunization with both primary and T-cell line adapted HIV-1. This study provides a rational basis for an alternative or complementary strategy of allo-immunization against HIV infection.

Previous xenogeneic immunization experiments in rhesus macaques with simian immunodeficiency virus (SIV) grown in human CD4؉ T cells consistently elicited protection from challenge with live SIV. However, the mechanism of protection has not been established. We present evidence that xenogeneic immunization induced significant CD8 suppressor factor, RANTES (regulated upon activation, normal T cell expressed and secreted), macrophage inf lammatory protein (MIP) 1␣, and MIP-1␤ (P < 0.001 -P < 0.02). The concentrations of these increased significantly in protected as compared with infected macaques (P < 0.001). Xenogeneic stimulation in vitro also up-regulated CD8 suppressor factors (SF; P < 0.001) and the ␤ chemokines which were neutralized by antibodies to the 3 ␤ chemokines. Recombinant human RANTES, MIP-1␣ and MIP-1␤ which bind to simian CCR5, suppressed SIV replication in a dose-dependent manner, with RANTES being more effective than the other two chemokines. The results suggest that immunization with SIV grown in human CD4 ؉ T cells induces CD8-suppressor factor, RANTES, MIP-1␣ and MIP-1␤ which may block CCR5 receptors and prevent the virus from binding and fusion to CD4 ؉ cells.