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. Sixty nine patients with metastatic cancer were treated with anticancer lymphocytes during the last year. Twelve different clinical trials are currently devoted to these treatments, as of September, 2008, 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. Finally, the core laboratory continues to process cells and serum collected from cancer patients for a variety of uses. The products serve as the precursor cells for generating the anticancer cells 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) identifying new cancer antigens that may be recognized by patients anticancer cells, 3) evaluating the ability of infused anticancer lymphocytes to survive and function in the patient, and 4) identifying characteristics of infused anti-cancer T cells that cause cancer regression as measured by standardized, objective criteria.
| Dudley, Mark E (2012) A major player ""gets in the act"". J Immunother 35:595-7 |
| Ahmadzadeh, Mojgan; Johnson, Laura A; Heemskerk, Bianca et al. (2009) Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114:1537-44 |
| Johnson, Laura A; Morgan, Richard A; Dudley, Mark E et al. (2009) Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:535-46 |
