An in vitro model for purging of tumour cells from ovarian tissue

Hum Reprod. 2004 May;19(5):1069-75. doi: 10.1093/humrep/deh244. Epub 2004 Apr 7.

Abstract

Background: Cryopreservation and autografting of ovarian tissue may preserve fertility after cancer treatment, but could be hampered by tumour cell contamination. Epithelial tumour cell lysis can be obtained with cytotoxic T cell retargeting through the bispecific antibody BIS-1, with combined affinity for the T-cell receptor and epithelial glycoprotein-2 (EGP-2). Our aim was to study the concept of tumour cell purging in the setting of a suspension of ovarian tissue.

Methods: Human ovarian tissue was brought into suspension by mechanical and enzymatic treatment. Cells of the MCF-7 breast cancer cell line and activated human lymphocytes were co- incubated for 4 h with or without BIS-1 and with or without ovarian suspension. After incubation, MCF-7 cell death and cell growth were evaluated by fluorescent cell detection and MTT assay, respectively. Ovarian tissue morphology was evaluated immunohistochemically.

Results: MCF-7 cell death and cell growth inhibition increased with increasing ratios of lymphocytes to MCF-7 cells. BIS-1 addition gave further augmentation, with a maximum depletion of growing MCF-7 cells of 89% (SD 11%) versus without BIS-1, 23% (SD 15%; P < 0.001). Follicles remained morphologically intact.

Conclusions: Purging of added epithelial tumour cells from ovarian tissue with BIS-1 is possible in vitro. Morphologically, follicles remain intact after this procedure. This method may contribute to safer replacement of ovarian tissue in female cancer survivors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bispecific
  • Breast Neoplasms / immunology
  • Breast Neoplasms / prevention & control
  • Cell Death
  • Cell Line, Tumor
  • Cell Separation / methods*
  • Cryopreservation
  • Epithelial Cells / pathology
  • Female
  • Humans
  • In Vitro Techniques
  • Infertility, Female / therapy
  • Ovarian Follicle / cytology*
  • Ovarian Follicle / pathology
  • Ovarian Follicle / transplantation*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / prevention & control*
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • Transplantation, Autologous

Substances

  • Antibodies, Bispecific