A Phase II Study of Tumor-infiltrating Lymphocyte Therapy for Human Papillomavirus-associated Epithelial Cancers

Clin Cancer Res. 2019 Mar 1;25(5):1486-1493. doi: 10.1158/1078-0432.CCR-18-2722. Epub 2018 Dec 5.

Abstract

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.

Patients and methods: The trial was a phase II design with two cohorts, cervical cancers and noncervical 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 of 18 (28%) patients in the cervical cancer cohort and 2 of 11 (18%) patients in the noncervical cancer cohort. Two of the responses in cervical cancer were complete and are ongoing 67 and 53 months after treatment. Responses in the noncervical 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: 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Carcinoma / diagnosis
  • Carcinoma / etiology*
  • Carcinoma / metabolism
  • Carcinoma / therapy*
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Middle Aged
  • Papillomaviridae*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Tomography, X-Ray Computed
  • Treatment Outcome