The purpose of this core resource facility is to provide ongoing support for the clinical immunotherapy program in the Surgery Branch of the National Cancer Institute. The laboratory is managed by two co-investigators, Drs. Mark Dudley and John Wunderlich, and each investigator has submitted the same annual report. The major effort in the laboratory is producing, ex vivo, large numbers of human anticancer T lymphocytes that are used in adoptive cell therapy for patients enrolled in Surgery Branch clinical trials. All of the patients have metastatic cancer, primarily melanoma. Commonly, ten to fifty billion cells are used for each treatment. The anticancer cells are generated in vitro from each patient's lymphocytes. The lymphocytes have natural anticancer activity, or anticancer activity induced or enhanced by genetic modification of the cells in vitro. Seventy six patients with metastatic cancer have been treated with anticancer lymphocytes during FY12 through August 1. During part or all of this same period of time, twenty one different clinical trials devoted to these therapies have been active and supported by the core laboratory.The core laboratory has also carried out research activities to improve its services. Thus, efforts have continued 1) to simplify the cell production methodology and make the process easier and more cost effective, 2) to relate characteristics of the anticancer lymphocytes and their parent populations to clinical outcomes following their use for treating patients, and 3) to help translate preclinical adoptive immunotherapy models, developed in the Surgery Branch and elsewhere, into new clinical protocols. Finally, the core laboratory continues to process cells and sera collected from cancer patients for a variety of uses, in addition to generating the anticancer cells described above. The products are routinely analyzed by investigators in the Surgery Branch immunotherapy program to evaluate progress toward the goals of each immunotherapy clinical trial, as well as to address subsequent research questions that help identify changes needed in the clinical trials. The samples are also used by Surgery Branch investigators for specific laboratory research projects that may translate into new patient therapies. These research projects include 1) transducing patients T cells with new genes whose products will provide better tumor recognition or otherwise enhance the cells anticancer functions, 2) evaluating the ability of infused anticancer lymphocytes to survive and function in the patient, 3) identifying new cancer antigens that are recognized by patients anticancer cells, 4) identifying characteristics of infused anticancer T cells that relate to cancer regression as measured by standardized, objective criteria, 5) identifying common characteristics of patients with metastatic cancer who are more likely to respond to adoptive cell therapy, 6) evaluating selected biological response modifiers tested in Surgery Branch clinical trials, and 7) extending adoptive cell therapy to additional types of metastatic cancer (e.g., cancers of the gastrointestinal tract and cancers induced by human papillomavirus).

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Deniger, Drew C; Kwong, Mei Li M; Pasetto, Anna et al. (2017) A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma. Clin Cancer Res 23:351-362
Assadipour, Yasmine; Zacharakis, Nikolaos; Crystal, Jessica S et al. (2017) Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple-Negative Breast Cancer. Clin Cancer Res 23:4347-4353
Gros, Alena; Robbins, Paul F; Yao, Xin et al. (2014) PD-1 identifies the patient-specific CD8? tumor-reactive repertoire infiltrating human tumors. J Clin Invest 124:2246-59
Pos, Zoltan; Spivey, Tara L; Liu, Hui et al. (2014) Longitudinal study of recurrent metastatic melanoma cell lines underscores the individuality of cancer biology. J Invest Dermatol 134:1389-1396
Turcotte, Simon; Gros, Alena; Tran, Eric et al. (2014) Tumor-reactive CD8+ T cells in metastatic gastrointestinal cancer refractory to chemotherapy. Clin Cancer Res 20:331-43
Bartlett, Edmund K; Fetsch, Patricia A; Filie, Armando C et al. (2014) Human melanoma metastases demonstrate nonstochastic site-specific antigen heterogeneity that correlates with T-cell infiltration. Clin Cancer Res 20:2607-2616
Dudley, Mark E; Gross, Colin A; Somerville, Robert P T et al. (2013) Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol 31:2152-9
Beard, Rachel E; Abate-Daga, Daniel; Rosati, Shannon F et al. (2013) Gene expression profiling using nanostring digital RNA counting to identify potential target antigens for melanoma immunotherapy. Clin Cancer Res 19:4941-50
Friedman, Kevin M; Prieto, Peter A; Devillier, Laura E et al. (2012) Tumor-specific CD4+ melanoma tumor-infiltrating lymphocytes. J Immunother 35:400-8
Gros, Alena; Turcotte, Simon; Wunderlich, John R et al. (2012) Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma. Clin Cancer Res 18:5212-23

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