Cell Production Core Facility

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The mission of this core laboratory is to provide support to the immunotherapy program established by the Surgery Branch of the National Cancer Institute. Cell Production Facility (CPF) core is overseen by Dr. Hyunmi Halas. The main effort of the laboratory involves the production of large numbers of human anti-cancer T lymphocytes ex vivo, to treat patients with advanced metastatic cancer enrolled on Surgery Branch clinical trials. Cancer targeting lymphocytes are either isolated directly from biopsied material or are generated by genetically modifying T lymphocytes from a patient's blood. The Surgery Branch Cell Prep (TIL Lab/CPF) Core receives patient tumors and blood products for processing as outlined in project ZIC BC 010905. These biological materials are used in the by the NCI SB researchers in the discovery of patient specific neoantigens and reactive tumor infiltrating lymphocytes (TILs). Once patient specific neoantigens or TILs are identified, a unique patient cellular therapy can be manufactured by the CPF core. 43 treatments were initiated during the reporting period. Four manufacturing runs represent two sets of two products designed for two patients. 4 were terminated due to manufacturing/reagent related issues while 4 runs were terminated due to clinical reasons. 30 treatments were delivered to patients, 17 on gene therapy protocols and 13 on TIL related protocols. Each product is a 24-day manufacturing run requiring 2 technicians, QA staff, supervisory oversight and 4 support staff members. All products are manufactured in the T30 CPF on the NIH Bethesda campus under cGMP conditions as outlined in the Code of Federal Regulations and the FDA for Phase 1 and 2 products. All starting materials are generated by the Surgery Branch Cell Prep (TIL Lab/CPF) Core and moved into manufacturing for the Cell Production Core Facility once patients are enrolled on clinical protocols. All post treatment follow-up samples collected from patients are inventoried by and largely processed by the Cell Production Core Facility. These materials are managed by the Cell Production Core Facility team though the NCI SB Biorepository, which contains thousands of samples onsite and many more at offsite locations. All requests for materials for research and tracking needs throughout the branch are received and distributed by Cell Production Core Facility. In addition to manufacturing cellular therapies, the Cell Production Core Facility ensure the facility, all equipment, and materials used in manufacturing are meeting cGMP regulations. This requires constant reporting, documentation and review of each processing step, and a log of all materials (biological and raw materials). The core lab also performs routine environmental monitoring of the facility (performed with the services from DLM Sterility Lab) and during every aseptic processing event. The Quality Assurance oversight requires a personnel training program that ensures competency and emphasizes the responsibilities and duties of all personnel involved in manufacturing cell therapies in the Surgery Branch. The core lab staff train all new technicians for manufacturing processes under these requirements and undergo annual re-training as well. The facilities, staff, and QMS is audited minimally on an annual basis by third party vendors through NIH Office of Research and Compliance or through internal NCI SB QA audits. The former primary cell production facility 3W/TIL lab is no longer used for manufacturing as of Dec 2020. New facilities have been qualified and validated for cGMP cellular manufacturing on the NIH campus. These include Trailer 10B, which will provide clinical cell supporting capabilities; 1B42 in building 10, which will support viral vector manufacturing; and T30, a 5000 square foot modular building that will serve as the main manufacturing facility for Surgery Branch Cell Therapies, which was completed in March 2021. Cell Processing Facility staff were actively involved in the review of all design and construction documents as well as in drafting and reviewing the commissioning documentation that is being generated for these facilities and are responsible for the cGMP operations of these facilities. The facility opened with approve from the NIH and FDA in 2022 and has since been operational for manufacturing and tissue processing.