Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers

Abstract

Purpose: To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of antitumor immunity to measure and which assays are optimal for those measurements.Experimental Design: The iSBTc-SITC (International Society for Biological Therapy of Cancer-Society for Immunotherapy of Cancer), FDA (Food and Drug Administration), and NCI (National Cancer Institute) partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions, and present our recommendations.Results and Conclusions: Although specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise, and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA (quality assessment)/QC (quality control) should be conducted and selected examples of truly representative raw data and assay performance characteristics should be included. Finally, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary

An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells

“…Finally, the different classes of biomarkers that are relevant to T-cell therapy trials have to be identified (Lacey et al, 2013). Accordingly, a CAR-T-19 cell clone was engineered for adoptive therapeutic use against cancer, and there is increasing interest in identification of sensitive, robust, and meaningful biomarkers that may provide relevant insights into the clinical development process Butterfield et al, 2011).…”

Therapeutic cancer vaccines: a long and winding road to success

“…Assays for quantifying vaccinespecific and/or vaccine-induced responses mainly include DTH, multimer staining for MHC-tumor peptide, cytotoxicity, T-cell proliferation assays, ELISA for tumor protein-specific antibodies and ELISPOT assays that detect IFN-g producing T cells. Analysis of immune cell subsets from PBMCs has recently been performed in some studies including, in addition to T-cell and antibody responses, quantitation of Tregs, MDSCs, NK cells and DCs [22,78,79]. Most of these assays are being studied in different clinical trials and in many cases the detected immunological response was associated with improved clinical outcomes [22,32,80].…”

1086 IGHV1-69 as a Promising Candidate for the Development of a Shared Immunotherapy to B-cell Lymphomas

“…Some trials have analysed also the antibody response to TAA, or variations in the percentage of Treg, myeloid derived suppressor cells, NK and DCs, often evaluating the ratio of effector to regulatory cells. In addition, many studies have used analysis of multiple serum cytokines and chemokines [3,[93][94][95][96][97][98].…”

“…Some trials have analysed also the antibody response to TAA, or variations in the percentage of Treg, myeloid derived suppressor cells, NK and DCs, often evaluating the ratio of effector to regulatory cells. In addition, many studies have used analysis of multiple serum cytokines and chemokines [3,[93][94][95][96][97][98].The study from Di Nicola et al, for example, documented significant changes in Treg, NK and anti-tumor T-cell frequencies, and humoral responses in responding patients compared with non-responding ones. These observations indicate that the clinical responses observed after tumor-loaded DC-based vaccination may be the result of an active modulatory effect on different components of the immune system [55].…”