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. Eighty six patients on 17clinical trials have been treated with cell therapies generated by this core laboratory during FY15 through August 1st. Eighty three patients underwent resection to generate tumor infiltrating lymphocyte cultures for treatment and successful cultures were established for eighty of these patients. In addition to the labs manufacturing functions, research has 1) simplified and streamlined the manufacturing process resulting in cost savings 2) related characteristics of the anticancer lymphocytes and their parent populations to clinical outcomes 3) translated preclinical findings from other groups within the Surgery Branch in to novel clinical protocols 4) implemented a closed, fully cGMP compliant manufacturing process for one of clinical products for use by a CRADA partner in the commercialization of one this therapy 5) trained personnel from other institutions which are seeking to establish adoptive cell transfer therapy programs. 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC011569-02
Application #
9154346
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Kochenderfer, James N; Somerville, Robert P T; Lu, Tangying et al. (2017) Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels. J Clin Oncol 35:1803-1813
Goff, Stephanie L; Dudley, Mark E; Citrin, Deborah E et al. (2016) Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma. J Clin Oncol 34:2389-97
Brudno, Jennifer N; Somerville, Robert P T; Shi, Victoria et al. (2016) Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. J Clin Oncol 34:1112-21
Benz, Brian A; Nandadasa, Sumeda; Takeuchi, Megumi et al. (2016) Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. Dev Biol 416:111-122
Kochenderfer, James N; Dudley, Mark E; Kassim, Sadik H et al. (2015) Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 33:540-9
Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K et al. (2015) Persistence of CTL clones targeting melanocyte differentiation antigens was insufficient to mediate significant melanoma regression in humans. Clin Cancer Res 21:534-43
Tran, Eric; Ahmadzadeh, Mojgan; Lu, Yong-Chen et al. (2015) Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350:1387-90
Tran, Eric; Turcotte, Simon; Gros, Alena et al. (2014) Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344:641-5