CHARACTERIZATION OF HUMAN COLON-CANCER ANTIGENS RECOGNIZED BY AUTOLOGOUS ANTIBODIES

The screening of cDNA expression libraries derived from human tumors w ith autologous antibody (SEREX) has proven to be a powerful method for defining the structure of tumor antigens recognized by the humoral im mune system. In the present study, 48 distinct antigens (NY-CO-I-NY-CO -48) reactive with autologous IgG were identified by SEREX analysis in 4 patients with colon cancer. Sequencing analysis showed that 17 of t he cDNA clones were previously uncharacterized molecules and 31 repres ented known gene products. The individual cDNA clones were analyzed in the following manner: a search for mutations or other structural chan ges; an analysis of mRNA expression in a panel of normal tissues; and a frequency analysis of the antibody response to the expressed product in the sera of colon cancer patients and normal individuals. The init ial analysis showed NY-CO-13 to be a mutated version of the p53 tumor suppressor gene. Three of the 48 antigens showed a differential patter n of mRNA expression, with NY-CO-27 (galectin-4) expressed primarily i n gastrointestinal tract, and NY-CO-37 and -38 showing a pattern of ti ssue-specific isoforms. With regard to immunogenicity, 20 of the 48 an tigens were detected by allogeneic sera; 14 of these were reactive wit h sera from both normal donors and cancer patients, and 6 other clones (NY-CO-8, -9, -13, -16, -20 and -38) reacted exclusively with sera fr om colon cancer patients (ranging from 14% to 27%). Our results on col on cancer illustrate both the complexity and the potential of the SERE X approach for analysis of the humoral immune response against human c ancer. (C) 1998 Wiley-Liss, Inc.