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. Robert Somerville and John Wunderlich, 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 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. Forty-three cell products were delivered to patients enrolled on 14 trials have been treated with cell therapies generated by this core laboratory during FY16 through August 1st. Sixty-eight 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) Extending anticancer cell therapies to other cancer histologies (lung, ovarian, breast and bladder cancers). 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. An audit of the cell production facility in March of 2106 resulted in the identification of several structural issues. The cell production facility was temporarily closed at the end of April 2016 and was reopened at the end of June 2016 after these issues had been addressed. During the closure, the HVAC system was upgraded to provide the approved number of air changes per hour, the appropriate differential air pressures between rooms within the facility and the air filtration was upgraded to ensure that particulate levels meet the specifications for manufacturing cell products. During the closure, surgery branch cell processing facility staff developed new procedures and documentation to augment existing programs, bringing the program into compliance with cGMP regulations.
