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, Drs. John Wunderlich and Robert Somerville, and each investigator has submitted 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 in 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 cell products, delivered to patients enrolled on 14 trials, were used to treat patients with cell therapies generated by this core laboratory during FY17 through August 1st. 57 patients underwent resection to generate tumor-infiltrating lymphocyte cultures for treatment, and successful cultures were established for sixty-four of these patients. A second critical function of this core lab is to collect, process, and curate samples from patients enrolled on 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 portion of the clinical translation of anticancer cell therapies carried out in the core lab. 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 data generated in the core lab is not lost as older file types become obsolete. In response to two independent audits of the Surgery Branch cell production facility in early 2016, several programs and systems have been developed to comply with NIH, FDA and industry guidance/best practices. Under a memorandum of understanding with the department of transfusion medicine (DTM), we have established an independent Quality Assurance (QA) program. This QA program functions independently of the cell processing facility and has the authority to stop production or prevent the release of cell-based therapies manufactured by the Surgery Branch cell processing facility when deemed necessary. Additionally, the QA program performs internal audits to ensure compliance with SOPs and procedures and approves the new employee and annual training of the facility staff. These programs ensure that patient safety, along with generating clinically effective anti-cancer cells, is a primary concern of all employees involved in the manufacture of cell-based therapies. A crucial component of the QA program is document control. A new document control system, MediaLab, has been implemented to ensure that all staff has access to the most update version of SOPs, forms, and regulations used by the cell processing facility. MediaLab allows full tracking of all document versions and changes to ensure better compliance and training for all cell processing facility SOPs and regulations. A cleaning service that specializes in cleanroom sanitation has been contracted to clean the facility, and the effectiveness of this program is tracked with a newly implemented environmental monitoring program that tracks and trends air and surface quality/cleanliness within the manufacturing areas of the facility. This program identifies potential sources of microbial contamination before they can impact the overall manufacturing operation. The final component of efforts to develop a robust QA system is the development of a materials management program. Materials management controls the acquisition, quarantine, acceptance, and release of all manufacturing materials. The goal of this program is to increase patient safety by improving documentation of source, lot number and expiration date and quality control of all materials used to manufacture cell products within the Surgery Branch cell processing facility. This program is crucial in identifying patient's whose past or pending treatments are associated with a manufacturer recall. The materials management program allows all patients impacted by a recall to be identified and monitored for adverse events.
