title: Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells.
abstract: OBJECTIVE
  Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer.
  
  
  METHODS
  Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin.
  
  
  RESULTS
  Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238).
  
  
  CONCLUSIONS
  Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted.
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stevanović
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Draper
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Langhan
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Tracy E
authors.initials: TE
authors.lastname: Campbell
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Mei Li
authors.initials: ML
authors.lastname: Kwong
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.affiliation: All authors: National Cancer Institute, Bethesda, MD. hinrichs@nih.gov.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hinrichs
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000628:therapy*
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