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Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody.

Publication ,  Journal Article
Osada, T; Hsu, D; Hammond, S; Hobeika, A; Devi, G; Clay, TM; Lyerly, HK; Morse, MA
Published in: Br J Cancer
January 5, 2010

BACKGROUND: Novel technologies to redirect T-cell killing against cancer cells are emerging. We hypothesised that metastatic human colorectal cancer (CRC) previously treated with conventional chemotherapy would be sensitive to T-cell killing mediated by carcinoembryonic antigen (CEA)/CD3-bispecific T-cell-engaging BiTE antibody (MEDI-565). METHODS: We analysed proliferation and lysis of CEA-positive (CEA+) CRC specimens that had survived previous systemic chemotherapy and biologic therapy to determine whether they could be killed by patient T cells engaged by MEDI-565 in vitro. RESULTS: At low concentrations (0.1-1 ng ml(-1)), MEDI-565+ T cells caused reduced proliferation and enhanced apoptosis of CEA+ human CRC specimens. High levels of soluble CEA did not impair killing by redirected T cells and there was no increase in resistance to T-cell killing despite multiple rounds of exposure. CONCLUSIONS: This study shows for the first time that metastatic CRC specimens derived from patients previously treated with conventional chemotherapy can be lysed by patient T cells. Clinical testing of cancer immunotherapies, such as MEDI-565 that result in exposure of tumours to large numbers of T cells, is warranted.

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Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

January 5, 2010

Volume

102

Issue

1

Start / End Page

124 / 133

Location

England

Related Subject Headings

  • fas Receptor
  • T-Lymphocytes, Cytotoxic
  • Oxaliplatin
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • Mice, Inbred NOD
  • Mice
  • Lymphocyte Activation
  • Liver Neoplasms
  • Humans
 

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Osada, T., Hsu, D., Hammond, S., Hobeika, A., Devi, G., Clay, T. M., … Morse, M. A. (2010). Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody. Br J Cancer, 102(1), 124–133. https://doi.org/10.1038/sj.bjc.6605364
Osada, T., D. Hsu, S. Hammond, A. Hobeika, G. Devi, T. M. Clay, H. K. Lyerly, and M. A. Morse. “Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody.Br J Cancer 102, no. 1 (January 5, 2010): 124–33. https://doi.org/10.1038/sj.bjc.6605364.

Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

January 5, 2010

Volume

102

Issue

1

Start / End Page

124 / 133

Location

England

Related Subject Headings

  • fas Receptor
  • T-Lymphocytes, Cytotoxic
  • Oxaliplatin
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • Mice, Inbred NOD
  • Mice
  • Lymphocyte Activation
  • Liver Neoplasms
  • Humans