Colonic Tumor CEA, CSAp and MUC-1 Expression following Radioimmunotherapy or Chemotherapy

Abstract

Understanding the changes in tumor biology following cytotoxic therapy may lead to a better understanding of the properties of surviving tumor cell populations and to an improved ability to target and treat these cells. This report addressed the time-dependent dynamic alterations in the expression of three tumor-associated antigens: carcinoembryonic antigen (CEA), colon-specific antigen (CSAp) and mucin-1 (MUC-1) following chemotherapy with 5-fluorouracil (5-FU) or radioimmunotherapy (RAIT; ¹³¹I-labeled anti-CEA IgG) in human colonic tumor xenografts. Immunoassay results show that CEA and MUC-1 expression all increase rapidly after either 5-FU or RAIT. GW-39 tumors show a 2.7-fold increase in CEA expression after a maximum tolerated dose of RAIT, being highest after 21 days, while LS174T and HT-29 tumors maximally increase expression 8.3- and 2.6-fold on day 7 after RAIT, respectively. The change in LS174T is short-term, whereas the change in HT-29 is maintained for at least 4 weeks. Serum CEA levels in these tumor- bearing mice also increase in parallel to the changes observed in tumor. MUC-1 increases 2.5-fold by day 5–7 following RAIT in LS174T tumors and 6-fold by day 14 following RAIT in GW-39 tumors, with a corresponding increase in serum MUC-1. Dramatic increases in CSAp after RAIT were also demonstrated in GW-39 tissue by immunohistochemistry. Thus, these data indicate that the response of tumor cells to low-dose-rate radiation from RAIT or to chemotherapy is associated with an increase of CEA, MUC-1 and CSAp.

Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria

“…Previous studies have shown that xenografts of the colorectal cancer cell line LS174T can be treated with an I-131-labeled anti-CEA antibody (14). We confirmed these results in two ways.…”

Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis

“…In addition, increased ICAM-1 expression could enhance immune destruction via direct costimulation of T cells, thus making tumor cells better immunogens. The tumor-associated antigens CEA and MUC-1 have previously been shown to be differentially expressed in tumors versus normal tissues (22). In addition, MHC class I molecule/peptide complexes are important for presentation of antigenic epitopes to T cells (40 -42).…”

“…There, irradiation alone significantly potentiated tumor rejection by antigen-specific CTL (55) and by vaccineinduced CTL (56). In another study, the dynamic changes in tumor antigen CEA expression in human colonic xenografts in response to radiation were investigated using radiolabeled antibodies (22). Immunohistology showed that radioantibody-delivered sublethal radiation (35 Gy) increased CEA expression in HT-29 and LS174T tumor xenografts.…”

Sublethal Irradiation of Human Tumor Cells Modulates Phenotype Resulting in Enhanced Killing by Cytotoxic T Lymphocytes

“…In addition, increased ICAM-1 expression could enhance immune destruction via direct costimulation of T cells, thus making tumor cells better immunogens. The tumor-associated molecules (TAA) CEA and MUC-1 are differentially expressed in tumors versus normal tissues (17), and MHC class I molecules are important for antigen presentation of tumor molecule epitopes to NOTE. Genes whose expression levels differed at least 3-fold between irradiated (at either 8 or 24 hours after irradiation) and nonirradiated WiDr cells were organized by their presumed function.…”

“…Although human colon, lung, and prostate are among the most prevalent cancers, very few studies, typically limited to one or two cell lines, have focused on the phenotypic changes in response to irradiation (17)(18)(19)(20)(21)(22). In addition, most of these studies examined changes in only one or two surface molecules.…”