Preclinical development and clinical monitoring of adoptive immune therapy

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

SUMMARY: The Preclinical Development and Clinical Monitoring Facility (PDCMF) of the Experimental Transplantation and Immunotherapy Branch supports the development and implementation of new protocols involving adoptive immune cell therapies through preclinical development, translational implementation of clinical products and preservation and analysis of patient blood and tissues during clinical trials. PDCMF staff, working within the Cell Processing Service of the Department of Transfusion Medicine, have documented patient data and aliquots of cells for RCR/RCL testing (15-C-0141, PI: James Kochenderfer; 20-C-0051, PI: Christian Hinrichs) for James Kochenderfer's Chimeric Antigen Receptor (CAR) therapies and for Christian Hinrichs's transgenic T cell products, in fulfillment of FDA requirements. As per our role in ZIC BC 010934, the PDCMF processes and preserves peripheral blood, marrow aspirates, and tumor biopsies, as well as the research aliquots of the starting and final cell products for this Project. We collaborate with the Cell Processing Service of DTM, the ETIB Flow Cytometry Facility, and ETIB T Cell Facility, and we routinely ship specimens to extramural labs for RCR/RCL testing and for a multicenter CRADA trial (16-C-0025, 16-C-0091, 19-C-0046; PI: James Kochenderfer). Our further contribution to the protocols can be distinguished on the basis of their principal investigators, James Kochenderfer and Christian Hinrichs. James Kochenderfer's clinical trials can be subdivided by the target molecules of their CAR constructs: CD30 (17-C-0048), CD19 (10-C-0054, 16-C-0054), BCMA (14-C-0168, 18-C-0125), and SLAM-F7 (19-C-0102). The manuscript described in the 2019 Annual Report was published in 2020, describing the clinical outcomes of 16-C-0054 and our characterization of CAR+ cells in the infusion product and in peripheral blood. Dr. Christian Hinrichs has therapeutic trials for treatment of viral-induced tumors, either by checkpoint inhibitors of the PD-1/PD-L1 system with or without TGFb blockade (16-C-0160 and 19-C-0002 and, in collaboration, 17-C-0125, PI: Mark Roschewski) or adoptive immunotherapy utilizing expanded T cells transduced to express a transgenic T cell receptor (16-C-0154, 17-C-0116, and 19-C-0091). The PDCMF has especially supported these protocols by the collection of tumor biopsies, in coordination with Dr. Hinrichs's researchers. The biopsies are sectioned and apportioned for downstream applications, such as viral genotyping, RNA-based analysis, and immunohistochemistry, with each requiring its own processing and storage conditions.