Abstract IA24: T cells as a drug for the personalized immunotherapy of cancer

Abstract

Abstract 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 24% 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 of treatment, 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. 81 of 99 patients with a variety of common epithelial cancers contained T cells that recognized the expressed products of 197 unique cancer mutations. Targeting these unique mutations opens the possibility of using ACT to treat patients with common epithelial cancers. In preliminary studies, we used this approach to treat a patient with metastatic cholangiocarcinoma using autologous mutation-reactive T cells and mediated durable regression of lung and liver metastases ongoing at five years. ACT using T cells that recognized the mutated KRAS oncogene product mediated objective regression of multiple lung metastases in a patient with metastatic colon cancer. Responses have also been seen in patients with metastatic cervical and breast cancer. 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 potentially be used to provide a highly personalized ACT immunotherapy 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 AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr IA24.