Validation of biomarkers to predict response to immunotherapy in cancer: Volume I — pre-analytical and analytical validation

摘要: Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1). Despite demonstrated in a variety malignancies, responses only typically occur minority any given histology. Additionally, treatment is associated inflammatory toxicity high cost. Therefore, determining which would derive benefit from immunotherapy compelling question. Although numerous candidate biomarkers described, are currently three FDA-approved assays based on PD-1 ligand expression (PD-L1) that clinically validated to identify who are more likely a single-agent anti-PD-1/PD-L1 therapy. Because complexity immune response tumor biology, it unlikely single biomarker will be sufficient predict outcomes immune-targeted Rather, integration multiple parameters, protein expression, genomics, transcriptomics, may necessary for accurate prediction clinical benefit. Before and/or new technology can used setting, several steps demonstrate its validity. regulatory guidelines provide general roadmaps validation process, their applicability cancer field somewhat limited. Thus, Working Group 1 (WG1) Society Immunotherapy Cancer (SITC) Immune Biomarkers Task Force convened address this need. In two volume series, we discuss pre-analytical analytical (Volume I) well II) aspects process applied predictive immunotherapy. To illustrate requirements validation, we discuss examples shown preliminary evidence an association immunotherapeutic interventions. The scope includes those technologies established certain level use (fit-for-purpose). Recommendations meet challenges strategies guide choice design specific also provided.