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Effect of yttrium‐90‐labeled anti‐carcinoembryonic antigen monoclonal antibody on the morphology and phenotype of human tumors grown as peritoneal carcinomatosis in athymic mice
Author(s) -
Esteban Jose M.,
Hyams David M.,
Beatty Barbara G.,
Wanek Phillip,
David Beatty J.
Publication year - 1989
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19890401)63:7<1343::aid-cncr2820630720>3.0.co;2-j
Subject(s) - carcinoembryonic antigen , medicine , pathology , monoclonal antibody , radioimmunotherapy , necrosis , peritoneal cavity , antibody , radiation therapy , antigen , cancer , immunology , surgery
Grossly visible peritoneal carcinomatosis resembling that seen in man was produced in athymic mice 7 days after intraperitoneal injection of 8 × 10 5 cells of the carcinoembrionic antigen (CEA)‐producing human colon carcinoma cell line LS174T. The mice received intraperitoneal injections of 40 to 160 μCi of yttrium‐90 ( 90 Y)‐labeled anti‐CEA monoclonal antibody (MAb). When the mice were killed 12 days after injection, a significant inhibition of tumor growth, ranging from 40% to 95%, was observed in the treated animals when compared to the growth of tumors in the untreated animals ( P < 0.001). No mortality secondary to the therapy was seen. The bone marrow was depleted significantly at the higher doses of labeled MAb, but total recovery was observed 4 weeks after treatment. Histologically, the treated tumors showed extensive radiation effects early in the posttherapy period and massive necrosis at later times. Minute foci of viable tumor remained in the periphery. New tumor outgrowths with histologic features similar to those in the untreated controls began to appear 3 weeks after therapy. The CEA expression of the treated tumors was similar to that of the untreated controls during the early posttreatment period, diminishing progressively as the tumors became necrotic. Newly grown tumor nodules in the treated animals lacked significant CEA expression both initially and at later times. Our studies suggest that therapy with 90 Y‐anti‐CEA MAb therapy results in selection of tumor clones lacking CEA, and that a single large dose of 90 Y‐MAb should be more effective than multiple fractions of smaller doses.