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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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Catumaxomab with Activated T-cells Efficiently Lyses Chemoresistant EpCAM-positive Triple-negative Breast Cancer Cell

Makoto Kubo1, Masayo Umebayashi2, Kanako Kurata1

  • 1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Anticancer Research
|July 5, 2018
PubMed
Abstract

Insights

Catumaxomab, a bispecific antibody, combined with activated T-cells effectively eliminated chemoresistant triple-negative breast cancer (TNBC) cells in vitro. This approach shows promise for treating EpCAM-positive TNBC, overcoming drug resistance.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Epithelial cell adhesion molecule (EpCAM) is a marker in various cancers, linked to metastasis and drug resistance.
  • Cancer stem-like cells in breast cancer express markers like CD44 and EpCAM.
  • Triple-negative breast cancer (TNBC) often exhibits chemoresistance and poor prognosis.

Purpose of the Study:

  • To investigate the efficacy of catumaxomab, a bispecific antibody, in combination with activated T-cells.
  • To determine if this combination can eliminate chemoresistant EpCAM-positive TNBC cells in vitro.

Main Methods:

  • Established a chemoresistant, EpCAM-positive TNBC cell line (MUK-BC1) from patient-derived cells.
  • Utilized catumaxomab to bridge EpCAM on tumor cells and CD3 on T-cells.
  • Activated autologous T-cells with interleukin-2/OKT3 for co-culture experiments.

Main Results:

  • The MUK-BC1 cell line demonstrated significant resistance to multiple chemotherapeutic agents.
  • Pre-treatment with catumaxomab followed by activated T-cells led to the elimination of EpCAM-positive TNBC cells.
  • The combination therapy proved effective against drug-resistant TNBC cells in vitro.

Conclusions:

  • Catumaxomab in combination with activated T-cells represents a potential therapeutic strategy for chemoresistant EpCAM-positive TNBC.
  • This approach may overcome therapeutic resistance in difficult-to-treat breast cancer subtypes.
  • Further investigation into this immunotherapy modality is warranted.
Keywords:
EpCAMcatumaxomabchemoresistancecytokine-activated T-cellstriple-negative breast cancer

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