Combined radioimmunotherapy and chemotherapy of breast tumors with Y-90-labeled anti-Her2 and anti-CEA antibodies with taxol.
Because breast cancer cells often express either Her2/neu or carcinoembryonic antigen (CEA) or both, these tumor markers are good targets for radioimmunotherapy using Y-90-labeled antibodies. We performed studies on nude mice bearing xenografts from MCF7, a cell line that has low Her2 and CEA expression, to more accurately reflect the more usual situation in breast cancer. Although uptake of In-111 anti-CEA into tumors was lower than that for In-111-labeled anti-Her2, radioimmunotherapy (RIT) with Y-90 anti-CEA was equivalent to that of Y-90 anti-Her2. When either Y-90 antibody was combined with a split-dose treatment with Taxol, the antitumor effect was greater than with either agent alone. When Y-90 anti-CEA was combined with a single dose of Taxol, the results were equivalent to the split-dose regimen. RIT plus cold Herceptin had no additional effects on tumor size reduction over RIT alone. When animals were first treated with Y-90 anti-Her2 and imaged 1-2 weeks later with In-111 anti-CEA or anti-Her2, tumor uptake was higher for anti-CEA and improved over tumor uptake with no prior RIT. These results suggest that a split dose of RIT with anti-Her2 antibody followed by anti-CEA antibody would be more effective than a single dose of either. This prediction was partially confirmed in a controlled study comparing single- vs split-dose anti-Her2 RIT followed by either anti-Her2 or anti-CEA RIT. These studies suggest that combined RIT and Taxol therapy are suitable in breast cancers expressing either low amounts of Her2 or CEA, thus expanding the number of eligible patients for combined therapies. They further suggest that split-dose RIT using different combinations of Y-90-labeled antibodies is effective in antitumor therapy.
Crow
Desiree M
DM
Department of Radioimmunotherapy, Division of Radiation Oncology, City of Hope National Medical Center, Duarte, California 91010, USA.
Williams
Lawrence
L
Colcher
David
D
Wong
Jeffrey Y C
JY
Raubitschek
Andrew
A
Shively
John E
JE
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000627:therapeutic use*; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000737:chemistry
D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D015021:Yttrium Radioisotopes