Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>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. To determine the antigens recognized by TIL we developed an approach based on deep exomic sequencing of the cancer and immunologic testing of TIL or peripheral lymphocytes to generate T cells that recognized immunogenic mutations. TIL from 34 patients with metastatic melanoma recognized 78 random somatic mutations, none of which were shared among different melanomas. We next extended these studies to patients with common epithelial cancers and showed that 64 of 84 (70%) patients with a variety of human cancer types, including esophageal, colorectal, bile duct, gastric, pancreatic, ovarian, cervical, and lung cancer, contained T cells that recognized 142 neoantigens, all of which were unique except for KRAS (3 patients) and p53 (4 patients). Targeting unique cancer mutations has extended the reach of ACT immunotherapy and was used to mediate objective regressions in selected patients with chemorefractory metastatic cancers of the bile duct, colon, cervix, and breast. 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 that can mediate durable cancer regressions in heavily pretreated patients with refractory lymphomas, sarcomas, and melanoma. Autologous T-cells can be used to provide a highly personalized immunotherapy for cancer patients refractory to conventional cancer treatments.</jats:p>
<jats:p>Citation Format: Steven A. Rosenberg. Keynote Lecture: Cell transfer immunotherapy targeting unique somatic mutations in cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr KN03.</jats:p>