The purpose of this core resource laboratory 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 immunotherapy for patients enrolled in Surgery Branch clinical trials. All of the patients have metastatic cancer, primarily melanoma but also human papilloma-induced cancers, synovial sarcoma, lymphoma, and others. Commonly, one to one hundred billion cells are used for each treatment. The anticancer cells are generated in vitro from each patients lymphocytes. The lymphocytes have natural anticancer activity, or anticancer activity induced or enhanced by genetic modification of the cells in vitro. One hundred fourteen patients with metastatic cancer have been treated with anticancer lymphocytes during FY13 through August 14. During part or all of this same period of time, fifteen 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 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, discovered in the Surgery Branch and elsewhere, into new clinical protocols. The core laboratory continues to process cells collected from cancer patients for a variety of uses. The collections serve as the precursor cells for generating the anticancer treatments described above. The products are routinely analyzed by investigators in the Surgery Branch immunotherapy program to help 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. In addition, the samples are 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 may be recognized by patients anticancer cells, 4) identifying characteristics of infused anti-cancer 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 ot 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). Finally, the Core Laboratory maintains and curates source documents, data, protocols, and expertise associated with cGMP manufacturing and clinical translation of cell therapies. Investigators within the Surgery Branch, intramural NCI laboratories, extramural regulatory agencies, industrial and academic collaborators, 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 #
1ZICBC011020-06
Application #
8763745
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$973,441
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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
Morgan, Richard A; Chinnasamy, Nachimuthu; Abate-Daga, Daniel et al. (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36:133-51
Wang, Anran; Chandran, Smita; Shah, Syed A et al. (2012) The stoichiometric production of IL-2 and IFN-γ mRNA defines memory T cells that can self-renew after adoptive transfer in humans. Sci Transl Med 4:149ra120
Uccellini, Lorenzo; De Giorgi, Valeria; Zhao, Yingdong et al. (2012) IRF5 gene polymorphisms in melanoma. J Transl Med 10:170
Seaman, Bradley J; Guardiani, Elizabeth A; Brewer, Carmen C et al. (2012) Audiovestibular dysfunction associated with adoptive cell immunotherapy for melanoma. Otolaryngol Head Neck Surg 147:744-9
Somerville, Robert P T; Devillier, Laura; Parkhurst, Maria R et al. (2012) Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVEýý bioreactor. J Transl Med 10:69
Somerville, Robert P T; Dudley, Mark E (2012) Bioreactors get personal. Oncoimmunology 1:1435-1437
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
Alvarez-Downing, Melissa M; Inchauste, Suzanne M; Dudley, Mark E et al. (2012) Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma. World J Surg Oncol 10:113
Dudley, Mark E (2012) A major player "gets in the act". J Immunother 35:595-7

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