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. Commonly, ten to fifty 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 and nine patients with metastatic cancer were treated with anticancer lymphocytes during the last year. Thirteen different clinical trials are currently devoted to these treatments, as of September, 2010, and are 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 melanoma who are more likely to respond ot adoptive cell therapy, 6) evaluating melanoma vaccines developed in the Surgery Branch and tested in clinical trials, and 7) evaluating selected biological response modifiers tested in Surgery Branch clinical trials. 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.

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National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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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
Zhang, Ling; Feldman, Steven A; Zheng, Zhili et al. (2012) Evaluation of ?-retroviral vectors that mediate the inducible expression of IL-12 for clinical application. J Immunother 35:430-9
Kvistborg, Pia; Shu, Chengyi Jenny; Heemskerk, Bianca et al. (2012) TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients. Oncoimmunology 1:409-418
Yao, Xin; Ahmadzadeh, Mojgan; Lu, Yong-Chen et al. (2012) Levels of peripheral CD4(+)FoxP3(+) regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer. Blood 119:5688-96
Kochenderfer, James N; Dudley, Mark E; Feldman, Steven A et al. (2012) B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119:2709-20
Bear, Adham S; Morgan, Richard A; Cornetta, Kenneth et al. (2012) Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? Mol Ther 20:246-9
Wang, Anran; Chandran, Smita; Shah, Syed A et al. (2012) The stoichiometric production of IL-2 and IFN-? mRNA defines memory T cells that can self-renew after adoptive transfer in humans. Sci Transl Med 4:149ra120
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
Friedman, Kevin M; Prieto, Peter A; Devillier, Laura E et al. (2012) Tumor-specific CD4+ melanoma tumor-infiltrating lymphocytes. J Immunother 35:400-8

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