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.
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.
Duke Scholars
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- fas Receptor
- T-Lymphocytes, Cytotoxic
- Oxaliplatin
- Organoplatinum Compounds
- Oncology & Carcinogenesis
- Mice, Inbred NOD
- Mice
- Lymphocyte Activation
- Liver Neoplasms
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- fas Receptor
- T-Lymphocytes, Cytotoxic
- Oxaliplatin
- Organoplatinum Compounds
- Oncology & Carcinogenesis
- Mice, Inbred NOD
- Mice
- Lymphocyte Activation
- Liver Neoplasms
- Humans