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 managed by two co-investigators, Dr. John Wunderlich and Robert Somerville with each investigator submitting the same annual report. 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. 27 cell products were delivered to patients enrolled on 13 trials have been treated with cell therapies generated by this core laboratory during FY18 through August 1st. 38 patients underwent resection to generate tumor-infiltrating lymphocyte cultures for treatment and successful cultures were established thirty-seven of these patients. 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 in response to two independent audits of the facility and its administrative systems in 2016. 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 hired 3 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. A subsequent audit by the ProPharma group in December of 2017 indicated that significant progress had been made in addressing the concerns of the initial audits and they highlighted programs/systems that needed strengthening or development. The existing cell manufacturing facilities are insufficient to support the expanding Surgery Branch Cell Therapy program. 3 New facilities are currently under construction or undergoing commissioning, Trailers 10A, and 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 when it opens in 2019. Cell Processing Facility staff are 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. As the buildings progress through the commissioning process, Surgery Branch personnel will be actively involved in all the process qualifications that are required to demonstrate that the new buildings/facilities can support the proposed manufacturing activities.
