IMR Press / EJGO / Volume 21 / Issue 1 / pii/2000104

European Journal of Gynaecological Oncology (EJGO) is published by IMR Press from Volume 40 Issue 1 (2019). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with S.O.G.

Original Research

Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7 - Pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix

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1 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Arkansas. Little Rock. AR, USA
2 Department of Nuclear Medicine. University of Arkansas. Little Rock. AR, USA
3 Department of Pathology, University of Arkansas, Little Rock, AR, USA
4 Department of Microbiology and Immunology, University of Arkansas, Little Rock, AR, USA
5 Division of Gynecologic Oncology, University of Brescia. Brescia, Italy
Eur. J. Gynaecol. Oncol. 2000, 21(1), 17–23;
Published: 10 February 2000

We describe a 27-year-old woman with systemic chemoresistant and radioresistant metastatic disease secondary to a recurrence of human papillomavirus (HPV) 18 infected cervical adenocarcinoma of the uterine cervix who received adoptive transfer of peripheral blood T cells stimulated with HPV 18 E7-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells derived from peripheral blood mononuclear cells (PBMC) included phenotypic analysis, cytotoxicity and intracellular cytokine production. High cytotoxicity activity was observed by CD8+T cells against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was significantly inhibited by pretreatment of tumor targets with MAb spe­cific for HLA class I as well as that of effector cells with anti-CDS, anti-LFA-1, but not anti CD3 MAb. Two-color flow cytometric analysis of the cytotoxic T cells revealed that a significant proportion of CDS+ cells was also CD56+. These double positive CTLs were thymically derived, as shown by expression of heterodimeric CDS molecules (α/β CD8) and were endowed with high cytotoxic activity against tumor cells. Analysis of intracellular cytokine expression showed that the striking majority of E7-pulsed DC activated CD8+T cells strongly expressed IFN-γ. TNF-α and IL-2 but not IL-4. The patient received two infusions of cytotoxic tumor-specific T cells at 2 week intervals, and in vivo distribution of the T cells was followed by111. In oxine labeling and serial gamma camera imaging. Persistent accumulation of radioactivity in the lungs, which harbored extensive metastatic disease, was detected up to 120 hrs after the infusion. Taken together, these results illustrate the potential of E7-specific and tumor-specific CTL­based immunotherapy for the treatment of patients with invasive cervical cancer. The abbreviations used are: HPV, Human Papillomavirus; MHC, Major Histocompatibility Complex; CTL, Cytotoxic T Lymphocyte; LCL, Lymphoblastoid B-cell line; DC; dendritic cells.

Cervical cancer
Dentritic cells
Adoptive immunotherapy
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