Doran SL, Stevanović S, Adhikary S, et al. - In this phase 1/2, single-center trial, researchers evaluated T-cell therapy as a treatment option for metastatic human papillomavirus (HPV)–associated epithelial cancers. Patients treated with prior platinum-based therapy for metastatic HPV16-positive cancer from any primary tumor site were included. Autologous genetically engineered T cells expressing a T-cell receptor directed against HPV16 E6 (E6 T-cell receptor T cells), a conditioning regimen, and systemic aldesleukin, constituted the treatment offered. Overall, 12 patients received treatment for metastatic HPV16-positive cervical (n = 6), anal (n = 4), oropharyngeal (n = 1), and vaginal (n = 1) cancer. The phase 1 portion revealed no dose-limiting toxicities. Objective tumor responses were reported in two patients, both in the highest dose cohort. Overall, epithelial cancer regression can be caused by engineered T cells. In the context of T-cell programmed death-1 expression and defects in interferon gamma and antigen presentation pathway components, tumor resistance was identified.