A variety of observations have shown that
carcinoembryonic antigen (CEA) is associated with growth and
metastasis of
cancers, including correlation of CEA serum levels with poor clinical outcome, mediation of cell-cell adhesion by CEA, and involvement of CEA in the immune recognition of
tumors and apoptotic pathways. The purpose of this study was to investigate the effect that an anti-CEA
monoclonal antibody (MAb) may have on the growth of
medullary thyroid cancer (MTC), a CEA-expressing
tumor, alone and in combination with
chemotherapy. Antitumor effects were evaluated in a nude mouse-human MTC xenograft model. Using the TT MTC cell line grown s.c., we compared
tumor growth in untreated mice with that of mice given the humanized anti-CEA MAb
labetuzumab or an isotype-matched control MAb. The effects of time of administration post-
tumor injection, MAb dose response, specificity of response, and combination with
dacarbazine (
DTIC)
chemotherapy were studied. The humanized anti-CEA MAb,
labetuzumab, has direct, specific, antitumor effects in this model, without conjugation to a
cytotoxic agent. In addition,
labetuzumab sensitizes these
tumor cells to
chemotherapy with an effective drug in this model,
DTIC, without increased toxicity. Significant delays in
tumor growth were caused by the MAb
therapy or
chemotherapy alone; however, the combination of these agents was significantly more effective than either agent given as a monotherapy or use of an irrelevant MAb in this model. The superiority of the combined modality treatment argues for the integration of CEA MAb
therapy into chemotherapeutic regimens for MTC management and possibly other CEA-expressing
neoplasms.