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. The laboratory 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. 32 patients each underwent a resection between 01-Aug-2021, 01-July, 2022. Of the 32 total resections processed by CPF, 16 resections were processed in the new Cell Production Facility (T30), which began clinical GMP manufacturing and processing on 24 Feb 2022. The 16 resections processed in T30 provided potential source of tumor-infiltrating lymphocytes (TIL) and 16 were research resection from which initial fragments as potential source of tumor-infiltrating lymphocytes (TIL) were not performed. 70% of the 16 resections processed for fragments and subsequent TIL cells during this time provided sufficient tumor tissue to provide 10+ fragments, which were cryopreserved. 3 patient resections yielded reactive fragments with tumor specific reactivity to generate TIL cell which can be expanded in culture cultures for potential treatments. 2 of these patients were resected in mid 2022 and most of the resections with expanded fragments are currently being screened for reactivity as potential future therapies. 4 patient resections were identified reactive fragments as well as candidates for gene modified T lymphocyte therapies. 5 patients were found to not have reactive fragments but were found to have reactive neoantigens for gene modified T lymphocyte therapies identified from the tumor resection and gene modified therapies to provide TCR known to recognize the cancer cells were identified. Nine(9) cell products, delivered to patients enrolled on 2 clinical trials, were used to treat patients with autologous cell therapies generated by this core laboratory since opening the new facility in Feb 2022 to July 2022. A second critical function of this core lab is to collect, process, and curate samples from patients enrolled in Surgery Branch protocols. These samples are used to generate the cancer therapies described above and are also used by investigators in the Surgery Branch cell therapy program to evaluate the progress of each clinical trial, as well as to address research questions that identify changes that can be implemented to improve these trials. In addition, the samples from these trials facilitate research that generates new patient therapies. These research projects include 1) Transducing patients' T cells with genes whose products will better target tumors or enhance endogenous tumor activity, 2) Evaluating the ability of infused anticancer lymphocytes to function and survive in patients, 3) Identifying new cancer-associated antigens that can be targeted by anticancer cells, 4) Identifying novel patient-specific antigens that are created by somatic mutations and selecting cultures that recognize these mutations for use in personalized T cell therapies 5) Identifying characteristics of infused anticancer cells that are associated with objective tumor regression, 6) Identifying characteristics of patients who are most likely to respond to anticancer T cell therapies, 7) Evaluating selected biological response modifiers tested in Surgery Branch clinical trials, 8) Evaluating new gene delivery systems such as the sleeping beauty transposon, 9) Producing dendritic cell vaccines that are pulsed with peptides representing a patient's own unique mutanome. Finally, the core laboratory maintains and curates all source documents, data, protocols, and expertise associated with cGMP manufacturing and the clinical translation of anticancer cell therapies. Due to the success of these therapies developed by the Surgery Branch, investigators within the Surgery Branch, intramural NCI laboratories, extramural regulatory agencies, industrial and academic partners, and other interested parties increasingly want access to these data, protocols, and advice. There is a need to develop new tools for curating data from older trials. There is a need to convert existing data into a format that can be read by newer software packages, it is essential that existing is not lost as older file types become obsolete. The Surgery Branch Cell Production Facility has implemented several programs since the development of a Quality Management Systems (QMS) in 2016 and oversight from the Office of Research Support and Compliance (ORSC). These programs include 1. Independent QA - Established through a memorandum of understanding with the Department of Transfusion Medicine who oversees the program. The program has a total of 7 QA specialists to manage the program. 2. Quality Management System (QMS) that governs all operations. 3. A materials management program to ensure that all products/materials that are used in the manufacture or come in to contact with patient therapies are of highest quality and free from adulteration. 4. An environmental monitoring program that ensures the facility is maintained in the highest possible state of cleanliness. 5. Equipment management program that ensures that all equipment used in manufacturing operations is functioning and is maintained appropriately. 6. A document management program that ensures all personnel are working from vetted and approved procedures. 7. 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 facilities and QMS is audited annually by third party vendors through ORSC. 3 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.