HPV-Associated Epithelial Cancer Tumors Regress With T-Cell Receptor Gene Therapy

Results from a recent clinical trial show that engineered T-cells can induce regression of human papillomavirus (HPV)-associated epithelial cancers (J Clin Oncol. 2019 Aug 13. Epub ahead of print).

Despite being an effective emerging cancer therapy, there are limited data supporting the use of genetically engineered T-cell therapy in epithelial cancers. This therefore warranted a proof-of-concept study by Stacey L. Doran, MD, National Institutes of Health, Bethesda, Maryland, and colleagues, who investigated the use of T-cell therapy in patients with metastatic HPV-associated epithelial cancers.

Between October 2014 and March 2016, a total of 12 patients with HPV16-positive cancer from any primary tumor site were enrolled in this phase 1/2 single-center trial at the National Cancer Institute. To be eligible, patients had to have received platinum-based therapy.

The primary end point was safety, and secondary end points were objective tumor response rate and duration of response. Patients were treated with autologous genetically engineered T-cells expressing a T-cell receptor directed against HPV16 E6 (ie, E6 T-cell receptor T-cells), a conditioning regimen, and systemic aldesleukin.

No patients in the phase 1 portion of the study experienced dose-limiting toxicities. One month posttreatment, all patients demonstrated high levels of peripheral blood engraftment, with a median of 30%.

A total of 2 patients had objective tumor responses. The majority of patients had tumor regression, though depth and duration varied; 1 patient with 3 lung metastases had complete regression of 1 tumor, and partial regression of the 2 others which were then resected.

Phase 2 of the trial was discontinued because the cell manufacturing supporting this clinical trial closed.

Of note, Dr Doran et al observed response and potential resistance to T-cell treatment, suggesting new challenges to develop effective T-cell therapies.

“Engineered 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,” they continued.

Dr Doran and colleagues concluded that these findings support continued investigation of genetically engineered T-cell therapy for epithelial cancers.—Kaitlyn Manasterski