Assessment of immune response in biotherapy trials and clinical endpoints

Abstract

Today, biological therapies occupy an important place among available clinical modalities for treatment of cancer. Their true impact on the disease cannot be unraveled, however, without an understanding of immune mechanisms that therapies target and possibly alter. Immune monitoring is necessary to help identify and defi ne these mechanisms. Recent introduction of rapid, high-throughput assays based on new insights into molecular pathways and attention to assay standardization has improved the quality of immune monitoring. Multiplex profi ling of immune phenotypes, defi nition of regulatory immune cell subsets, identifi cation of critical signaling molecules, and recognition of biologically relevant targets have all played a major role in defi ning immune competence of patients enrolled in biotherapy clinical trials. Today, the major objective of immune monitoring, to correlate therapy- induced alterations in immune responses and clinical endpoints, is fi nally being achieved, and potential immune biomarkers of disease-free or overall survival are being identifi ed. In most cases, validation of these immune biomarkers remains to be performed. There is hope that reliable immune biomarkers of response to biotherapy will soon emerge as a result of expert serial monitoring. Immune monitoring is critical to establishing surrogate biomarkers of outcome in biotherapy clinical trials and thus to a better selection and delivery of biologics to patients with cancer.