Publications [#178163] of Gayathri R Devi

Papers Published

1. T Osada, D Hsu, S Hammond, A Hobeika, G Devi, TM Clay, HK Lyerly, MA 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., British journal of cancer, vol. 102 no. 1 (January, 2010), pp. 124-33, ISSN 1532-1827 [doi]
   (last updated on 2010/08/09)

   Abstract:
   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.

   Keywords:
   Adenocarcinoma • Animals • Antibodies, Bispecific • Antigens, CD3 • Antigens, CD95 • Antineoplastic Combined Chemotherapy Protocols • Apoptosis • Carcinoembryonic Antigen • Colorectal Neoplasms • Cytotoxicity, Immunologic • Drug Resistance, Neoplasm • Fas Ligand Protein • Granzymes • Humans • Liver Neoplasms • Lymphocyte Activation • Mice • Mice, Inbred NOD • Organoplatinum Compounds • T-Lymphocytes, Cytotoxic • drug effects • drug therapy • immunology • immunology* • pathology • pharmacology • physiology • secondary* • therapeutic use