Toward the harmonization of immune monitoring in clinical trials: Quo vadis?

Excerpt

A constantly increasing number of cancer immunotherapies are being investigated in clinical trials but no reliable biomarkers to predict clinical benefit currently exist. For some cancer types, biomarkers have proven to be meaningful predictors of patient outcomes (e.g., BCR-ABL in Chronic Myeloid Leukemia or PSA in prostate cancer) and were established as routine tools. As effects of cancer immunotherapy are mediated through the immune system, immune responses may act as natural biomarkers for clinical efficiency if the right factors can be reliably measured. Following this concept, cancer immunotherapy trials over the last decade have often included measures of tumor-specific cellular immune responses as endpoints to identify reliable surrogates for clinical benefit. Substantial efforts were invested throughout the immunotherapy field in setting up suitable cellular immune assays. However, to date, data from clinical trials do not consistently show that immune responses are correlated with clinical endpoints [1]. This lack of correlation is partially interpreted as a consequence of the high variability in assay results, due to the lack of assay standardization, validation and harmonization across laboratories. If harmonization of immune assays can be achieved, assays can be tested as surrogate endpoints in clinical trials, substantially accelerate the development of immunotherapeutic agents and, in addition, offer a rationale to pre-select groups of patients with high probability to benefit from subsequent immunotherapy. …