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A focused immune response targeting the homotypic binding domain of the carcinoembryonic antigen blocks the establishment of tumor foci in vivo
Author(s) -
AbdulWahid Aws,
Huang Eric H.B.,
Lu Huixin,
Flanagan Jean,
Mallick Amirul Islam,
Gariépy Jean
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27582
Subject(s) - carcinoembryonic antigen , antibody , immune system , in vivo , cancer , cancer research , medicine , antigen , immunotherapy , immunology , pathology , biology , microbiology and biotechnology
Metastatic forms of cancers remain the main cause of death in cancer patients. In this study, we demonstrate that directing a sustained antibody response towards the homotypic binding function of CEA interferes with the implantation and development of tumor foci in CEA‐expressing transgenic (CEA.Tg) mice. Specifically, vaccinating CEA.Tg mice with a recombinant, altered self‐form of the CEA Ig V‐like N domain led to the production of circulating IgG1 and IgG2a antibodies that inhibited CEA‐mediated adhesion of murine carcinoma expressing CEA (MC38.CEA) and mediated antibody‐dependent lysis of tumor cells. Moreover, vaccinated CEA.Tg mice were resistant to the development of tumor nodules in the lungs and the peritoneal cavity, suggesting that mounting a focused antibody response to the CEA N domain may represent a simple therapeutic strategy to control the establishment of metastatic foci in cancer patients.