Adoptive cell transfer (ACT) immunotherapy using T lymphocytes with antitumor activity is a living therapy that can be highly effective in patients with a variety of metastatic cancers. Naturally occurring tumor infiltrating lymphocytes (TIL) expanded in vitro and administered following a lymphodepleting preparative regimen mediated objective regression of metastatic melanoma in 56% of 194 patients including complete regressions in 20% of patients who remain ongoing disease-free 3 to 10 years later. Recent studies have shown that TIL recognized random somatic mutations that served as the targets resulting in complete cancer regressions. To extend ACT immunotherapy to additional patients we developed an approach based on deep exomic sequencing and immunologic testing to generate T cells that recognized immunogenic mutations in a variety of human cancer types including esophageal, colorectal, bile duct, gastric, pancreatic, ovarian and lung cancer. Targeting these unique mutations opens the possibility of using ACT to treat patients with common epithelial cancers. We used this approach to treat a patient with metastatic cholangiocarcinoma using autologous mutation-reactive T cells and mediated regression of lung and liver metastases ongoing at two years. In addition to the use of naturally occurring mutation-reactive cells, we have genetically engineered autologous lymphocytes to express antitumor T-cell receptors (TCR) or chimeric antigen receptors (CAR) for use in ACT immunotherapy. These cells can mediate durable cancer regressions in heavily pretreated patients with refractory lymphomas, sarcomas, and melanoma. Thus autologous T cells can be used to provide a highly personalized therapy for cancer patients refractory to conventional cancer treatments.
Citation Format: Steven Rosenberg. T cells as a drug for the personalized immunotherapy of cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA01.
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