PURPOSEGenetically engineered T-cell therapy is an emerging treatment of hematologic cancers with potential utility in epithelial cancers. We investigated T-cell therapy for the treatment of metastatic human papillomavirus (HPV)–associated epithelial cancers.METHODSThis phase I/II, single-center trial enrolled patients with metastatic HPV16-positive cancer from any primary tumor site who had received prior platinum-based therapy. Treatment consisted of 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.RESULTSTwelve patients were treated in the study. No dose-limiting toxicities were observed in the phase I portion. Two patients, both in the highest-dose cohort, experienced objective tumor responses. A patient with three lung metastases experienced complete regression of one tumor and partial regression of two tumors, which were subsequently resected; she has no evidence of disease 3 years after treatment. All patients demonstrated high levels of peripheral blood engraftment with E6 T-cell receptor T cells 1 month after treatment (median, 30%; range, 4% to 53%). One patient’s resistant tumor demonstrated a frameshift deletion in interferon gamma receptor 1, which mediates response to interferon gamma, an essential molecule for T-cell–mediated antitumor activity. Another patient’s resistant tumor demonstrated loss of HLA-A*02:01, the antigen presentation molecule required for this therapy. A tumor from a patient who responded to treatment did not demonstrate genetic defects in interferon gamma response or antigen presentation.CONCLUSIONEngineered T cells can induce regression of epithelial cancer. Tumor resistance was observed in the context of T-cell programmed death-1 expression and defects in interferon gamma and antigen presentation pathway components. These findings have important implications for development of cellular therapy in epithelial cancers.

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Purpose Cellular therapy is an emerging cancer treatment modality, but its application to epithelial cancers has been limited. This clinical trial evaluated tumor-infiltrating lymphocyte (TIL) therapy for the treatment of patients with metastatic human papillomavirus (HPV)-associated carcinomas. Experimental Design The trial was a phase II design with two cohorts, cervical cancers and non-cervical cancers. Cell infusion was preceded by a lymphocyte-depleting conditioning regimen and followed by systemic high-dose aldesleukin. Results Objective tumor responses occurred in 5/18 (28%) patients in the cervical cancer cohort and 2/11 (18%) patients in the non-cervical cancer cohort. Two of the responses in cervical cancer were complete and are ongoing 67 and 53 months after treatment. Responses in the non-cervical cancer cohort were in anal cancer and oropharyngeal cancer. The HPV reactivity of the infused T cells correlated with clinical response. Peripheral blood repopulation with HPV-reactive T cells also correlated with clinical response. Conclusions/Discussion These findings support the concept that cellular therapy can mediate the regression of epithelial cancers, and they suggest the importance of predictive biomarkers and novel treatment platforms for more effective therapies.

Introduction Endovascular aortic repair has revolutionized the management of traumatic blunt aortic injury (BAI). However, debate continues about the extent of injury requiring endovascular repair, particularly with regard to minimal aortic injury (MAI). Therefore, we conducted a retrospective observational analysis of our experience with these patients. Methods We retrospectively reviewed all BAI presenting to an academic Level I trauma center over a ten-year period (2000–2010). Images were reviewed by a radiologist and graded according to Society for Vascular Surgery (SVS) guidelines (Grade I–IV). Demographics, injury severity, and outcomes were recorded. Results We identified 204 patients with BAI of the thoracic or abdominal aorta. Of these, 155 were deemed operative injuries at presentation, had grade III-IV injuries, or aortic dissection and were excluded from this analysis. The remaining 49 patients had 50 grade I–II injuries. We managed 46 grade I injuries (intimal tear or flap, 95%), and 4 grade II injuries (intramural hematoma, 5%) nonopertively. Of these, 41 patients had follow-up imaging at a mean of 86 days post-injury and constitute our study cohort. Mean age was 41 years and mean length of stay was 14 days. The majority (48 of 50, 96%) were thoracic aortic injuries and the remaining 2 (4%) were abdominal. On follow-up imaging, 23 of 43 (55%) had complete resolution of injury, 17 (40%) had no change in aortic injury, and 2 (5%) had progression of injury. Of the 2 patients with progression, one progressed from grade I to grade II and the other progressed from grade I to grade III (pseudoaneurysm). Mean time to progression was 16 days. Neither of the patients with injury progression required operative intervention or died during follow-up. Conclusions Injury progression in grade I–II BAI is rare (∼5%) and did not cause death in our study cohort. Since progression to grade III injury is possible, follow-up with repeat aortic imaging is reasonable.