Cancer Immunity 6:5 (2006)

Effects of desialylation of ovine submaxillary gland mucin (OSM) on humoral and cellular immune responses to Tn and sialylated Tn

Kevin P. O'Boyle¹, Susan Coatsworth², Gillian Anthony², Mark Ramirez², Edward Greenwald², Ronald Kaleya², Jacob J. Steinberg², Janice P. Dutcher¹, and Peter H. Wiernik¹

¹Our Lady of Mercy Cancer Center, New York Medical College, 600 E. 233rd Street, Bronx, NY 10466, USA
²Montefiore Medical Center, Albert Einstein College of Medicine, 111 E. 210th Street, Bronx, NY 10467, USA

Keywords: clinical trial, carcinoma, vaccination, ovine submaxillary gland mucin, sialylation, immunological monitoring, humoral immunity

Abstract

Resected carcinoma patients were immunized 3-5 times with ovine submaxillary gland mucin (OSM) containing predominantly sialylated Tn (sTn), completely desialylated ovine submaxillary gland mucin (dOSM) containing predominantly Tn, or 50% desialylated OSM containing Tn and sTn plus bacillus Calmette-Guerin (BCG) as an immunologic adjuvant. Pre- and postimmunization sera were quantified by ELISA, whole-cell ELISA, and immune stain dot blots. Fifteen of 17 patients produced IgG antibody titers from 40 to 5120 times more reactive with OSM and dOSM postimmunization. More importantly, these IgG antibodies reacted with LS-174T, a human colon carcinoma cell line. Significant DTH-like responses (1-17 cm) were observed in 15 of 17 patients; the strength of these responses was dependent on the presence or absence of sialic acid. Biopsies of these DTH-like reactions revealed infiltration with some CD8+ lymphocytes and mast cells. These results suggest that a single 9-carbon sugar can affect cellular immune responses to mucin antigens. It is thought that these large erythematous, nonindurated cellular reactions are antibody-mediated Arthus-like reactions. OSM, and especially dOSM, were also found to inhibit lymphocyte proliferation.