The critical role of the immune system in effecting anti-tumor responses to traditional and molecularly-targeted therapies is increasingly recognized, such that there is now an explosion of activity in the clinical investigation of immuno-oncology. In parallel, we have gained great advances in our ability to extract useful biologic information from patient material through the development of: (i) high-throughput DNA/RNA sequencing, that has uncovered major genetic determinants of clinically-evident immune responses; (ii) highly multiplexed biological assays, that have revealed the complex interplay between immunity and cancer in relation to therapy; and (iii) advanced computational methods, that have enabled large-scale integrative data analysis. Underlying this activity is a need to identify the critical biomarkers of response and resistance to therapy in each disease and across diseases. With the rapidly evolving clinical and experimental developments in immunotherapy occurring across all major academic centers, the need to build a coordinated infrastructure for data collection, processing and analysis has emerged as a high priority. At Dana-Farber Cancer Institute (DFCI), the Center of Immuno-Oncology (CIO) was established several years ago and is a local hub of translational immuno-oncology activity. As a part of its mission, the CIO supports dedicated translational biomarker laboratories to provide expertise in the analysis of immune correlatives in the service of immuno-oncology trials. Collectively, these resources provide multidisciplinary capabilities supporting both investigator-initiated and externally-sponsored studies ranging from clinical trial design, the performance of well-validated immune monitoring capabilities on patient samples during trials, the interpretation of data from immune monitoring testing, and the development of novel assays based on the scientific questions motivated by individual clinical studies. We propose to expand the laboratory and biostatistical capabilities of the CIO along with those of additional DFCI units as a Cancer Immune Monitoring and Analysis Center (CIMAC). We want to coordinate the efforts of the proposed DFCI-CIMAC with other CIMACs and with the Cancer Immunologic Data Commons (CIDC) to develop the standards for designing studies rich with immune correlatives and informative for candidate biomarkers, to be tested in future trials.
Aim 1 focuses on harmonizing the technical aspects of assays offered by the CIMACs;
Aim 2 focuses on the assay-specific scoring analyses and reporting of CIMAC offerings. Modeled on our long history of implementing standard and innovative assays to study DFCI phase I/II trials, we describe a process for using `Tier 1' `shovel-ready' assays that we expect as standard components of an immune monitoring tool-kit and `Tier 2' assays that are tailored to the specific needs of a study (Aim 3). Altogether, these efforts fall within the concept and vision of personalized medicine for immuno-oncology because only by the analyses of large well-annotated datasets can we identify links between biology, molecular markers and clinical response.
There has been recent rapid expansion of immunotherapy clinical trials to treat patients with cancer as well as of the types of sophisticated tests that can be applied to patient blood and tissues collected as part of these clinical trials that promise to provide deep insights regarding why these treatments are effective. The goal of this application is to develop a specialized center with expertise in the important area of new clinical trials and in how we can learn from these trials based on the application of a battery of molecular, pathology and immunologic assays to these samples. We leverage long track record of experience in this area, having performed these types of analyses for our local studies, to now contribute to the creation of a network of similarly-oriented centers to support, harmonize, compare, and disseminate existing and new approaches for learning of the mechanisms underlying responses to immune-based therapies for the treatment of cancer.