Treatment of metastatic human papillomavirus-associated epithelial cancers with adoptive transfer of tumor-infiltrating T cells.

3004 Background: Adoptive T-cell therapy (ACT) is a promising cancer treatment modality. However, its study in epithelial cancers has been limited. Human papillomavirus (HPV)-associated cancers are difficult to treat epithelial malignancies for which better systemic treatments are needed. We conducted a clinical trial of ACT for the treatment of metastatic HPV-associated cancers. Methods: The clinical trial was a phase II design with two disease cohorts (cervical cancers and non-cervical cancers). Patients were treated with a single infusion of tumor-infiltrating lymphocytes (TIL), which were generated, when possible, from TIL subcultures with HPV-oncoprotein reactivity (HPV-TIL). HPV-TIL infusion was preceded by a lymphocyte-depleting conditioning regimen 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. In the cervical cancer cohort, two patients experienced complete responses that are ongoing 53 and 67 months after treatment. Three patients experienced partial responses that were three months in duration. In the non-cervical cancer cohort, partial responses were observed in a patient with anal cancer (four months duration) and a patient with oropharyngeal cancer (five months duration). The latter patient had previously been treated with six systemic anti-cancer agents. Multiple thoracic metastases responded completely after HPV-TIL infusion. A brain metastasis developed five months after treatment and was surgically resected. He is without evidence of disease 51 months after treatment. Conclusions: HPV-TIL can mediate regression of metastatic HPV-associated cervical, oropharyngeal and anal epithelial cancers in some patients. These findings support the study of ACT for HPV-associated cancers and possibly other epithelial malignancies. Clinical trial information: NCT01585428.