CELL-MEDIATED CYTOTOXICITY OF HUMAN COLON-CARCINOMA CELLS BY A MONOCLONAL-ANTIBODY (R4) RECOGNIZING THE CARCINOEMBRYONIC ANTIGEN (CEA) AND CEA-RELATED MOLECULES
R. Bei et al., CELL-MEDIATED CYTOTOXICITY OF HUMAN COLON-CARCINOMA CELLS BY A MONOCLONAL-ANTIBODY (R4) RECOGNIZING THE CARCINOEMBRYONIC ANTIGEN (CEA) AND CEA-RELATED MOLECULES, International journal of oncology, 8(6), 1996, pp. 1127-1135
We report a novel anti-CEA monoclonal antibody (MAb) designated R4, wh
ich mediates antibody-dependent cell-mediated cytotoxicity (ADCC) of h
uman colon carcinoma cells and displays differential reactivity for hu
man carcinomas versus the normal counterparts. R4 (IgG1) reacted with
the cell surface of 6 colon carcinoma cell lines expressing CEA. Weste
rn blot analysis and epitope mapping using native and baculovirus reco
mbinant CEA and non specific cross-reacting antigen (NCA) demonstrated
that MAb R4 recognizes a proteinic epitope located on the 3' end of t
he domain I shared by CEA and NCA molecules. Immunohistochemical analy
sis demonstrated an intense staining of MAb R4 with the majority of th
e neoplastic tissues tested, including colon (13/13), stomach (2/2), b
reast (9/10), lung (7/10) and endometrial (2/4) carcinomas, whereas no
reactivity with the correspondent normal tissues was observed. Using
human PBLs from healthy donors as effector cells, we have shown that M
Ab R4 mediated antibody dependent-cell mediated cytotoxicity (ADCC) of
human carcinoma cells LS-174T, CBS and WiDr. This activity was enhanc
ed after PBLs activation with interleukin-2 (IL-2). The specificity of
MAb R4 for an epitope shared by two tumor overexpressed antigens, CEA
and NCA, resulting in an intense reactivity with neoplastic cells and
the peculiar property to mediate ADCC, indicate that MAb R4 might be
a novel powerful reagent for diagnostic and immunotherapy of carcinoma
patients.