The Preclinical Development and Clinical Monitoring Facility (PDCMF) of the Experimental Transplantation and Immunology 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 for James Kochenderfer's Chimeric Antigen Receptor (CAR) therapies (protocols 10-C-0054, 14-C-0168, 16-C-0054, 17-C-0048, 18-C-0125), in fulfillment of FDA requirements. PDCMF staff have also helped to optimize the generation of cell products (Greene, et al 2019) and to prepare the IND application and preclinical validation to bring new cell products to clinical trial under GMP conditions. Notable contributions in 2019 include the validation of reagents for a new anti-SLAMF7 CAR product (19-C-0102, PI: James Kochenderfer). 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; 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), and BCMA (14-C-0168, 18-C-0125, 19-C-0102). Our contributions to a manuscript describing the clinical outcomes of one of the CAR trials is similar to our work last year, characterizing the CAR+ cells in the infusion product and at their peak level in the in patients enrolled in 14-C-0168. Dr. Christian Hinrichs has initiated 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 and19-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 and 17-C-0116). 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.
