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Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells

Journal of clinical oncology, 2015-05, Vol.33 (14), p.1543-1550 [Peer Reviewed Journal]

Published by the American Society of Clinical Oncology. ;Published by the American Society of Clinical Oncology 2015 American Society of Clinical Oncology ;ISSN: 0732-183X ;EISSN: 1527-7755 ;DOI: 10.1200/JCO.2014.58.9093 ;PMID: 25823737

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  • Title:
    Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells
  • Author: Stevanović, Sanja ; Draper, Lindsey M ; Langhan, Michelle M ; Campbell, Tracy E ; Kwong, Mei Li ; Wunderlich, John R ; Dudley, Mark E ; Yang, James C ; Sherry, Richard M ; Kammula, Udai S ; Restifo, Nicholas P ; Rosenberg, Steven A ; Hinrichs, Christian S
  • Subjects: Adult ; Aged ; Alphapapillomavirus ; Female ; Human papillomavirus ; Humans ; Lymphatic Metastasis ; Middle Aged ; ORIGINAL REPORTS ; Remission Induction ; T-Lymphocytes, Cytotoxic ; Uterine Cervical Neoplasms - pathology ; Uterine Cervical Neoplasms - therapy
  • Is Part Of: Journal of clinical oncology, 2015-05, Vol.33 (14), p.1543-1550
  • Description: 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. 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. 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). 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.
  • Publisher: United States: American Society of Clinical Oncology
  • Language: English
  • Identifier: ISSN: 0732-183X
    EISSN: 1527-7755
    DOI: 10.1200/JCO.2014.58.9093
    PMID: 25823737
  • Source: GFMER Free Medical Journals
    MEDLINE
    Alma/SFX Local Collection
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