Correlative Science

Stanford University, Stanford CA

Investigators

Linked publications & trials

Abstract

Abstract Core C will provide biobanking, data and metadata analysis pipelines, and novel correlative assays for each of the proposed projects. The planned Core C aims are a natural extension of previous biobanking and correlative assay development and implementation activities in the Stanford Division of Blood and Marrow Transplantation and Cellular Therapy (BMT-CT). The BMT-CT Biobank currently manages the collection, storage, and distribution of tissue specimens for translational research on IRB-approved tissue repository protocols. Since the Biobank’s inception, tissue samples have been collected longitudinally from patients undergoing hematopoietic cell transplantation, as well as all related and unrelated allogeneic donors. Recently, BMT-CT biobanking efforts were expanded to include patients treated on investigator-initiated chimeric antigen receptor T cell (CAR T) trials, as well as standard-of-care and selected industry-sponsored CAR T cell therapy trials. Over 100,000 plasma and 85,000 PBMC samples are currently stored in the BMT-CT Biobank, and the continuation of these successful biobanking efforts will provide an essential resource for ongoing and future correlative research. BMT-CT investigators also have a proven history of developing and implementing human correlative PK/PD assays in the transplantation and cell therapy space. We have recently utilized single cell RNA sequencing (scRNA-Seq) approaches for characterization of CAR T cell biology ex vivo as well as CAR T cell efficacy, durability, and safety in vivo. However, the application of this and other multiparametric, data-intensive techniques is limited by highly complex data analysis requirements. We have created a large, multi-cloud clinical trial data platform that orchestrates the ingestion and harmonization of patient data from over a dozen sources and stakeholders – ranging from patient clinical attributes obtained from the hospital EMR system to molecular assays like qPCR and scRNA-Seq. We are now proposing to continue the development of this automated pipeline to increase the efficiency of data analysis and transform the application of single cell sequencing and other multiparametric approaches in the academic setting. Finally, we are collaborating with Stanford Pathology using our dedicated multiplexed single cell imaging platform. This method allows simultaneous evaluation of 30-100 antigens from the planar surface of a single tissue slide and enables deep profiling of complex lymphoma and other tumor samples with complicated combinations of antigen expression. We intend to utilize this imaging and spatial analysis platform for Stanford BMT-CT translational research projects and will prioritize projects identified in this program project. In summary, this Core will continue to support and enhance the established biobanking operations, data analysis infrastructure, and correlative analyses provided by the BMT-CT Division. The proposed Core C activities will enable project investigators to scientifically monitor transplantation and cellular therapy clinical trials and will ultimately advance our understanding of the correlatives of clinical response in these important studies.