Schlereth, Bernd;
Fichtner, Iduna;
Lorenczewski, Grit;
Kleindienst, Petra;
Brischwein, Klaus;
da Silva, Antonio;
Kufer, Peter;
Lutterbuese, Ralf;
Junghahn, Ilse;
Kasimir-Bauer, Sabine;
Wimberger, Pauline;
Kimmig, Rainer;
Baeuerle, Patrick A.
Eradication of Tumors from a Human Colon Cancer Cell Line and from Ovarian Cancer Metastases in Immunodeficient Mice by a Single-Chain Ep-CAM-/CD3-Bispecific Antibody Construct
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Medientyp:
E-Artikel
Titel:
Eradication of Tumors from a Human Colon Cancer Cell Line and from Ovarian Cancer Metastases in Immunodeficient Mice by a Single-Chain Ep-CAM-/CD3-Bispecific Antibody Construct
Beteiligte:
Schlereth, Bernd;
Fichtner, Iduna;
Lorenczewski, Grit;
Kleindienst, Petra;
Brischwein, Klaus;
da Silva, Antonio;
Kufer, Peter;
Lutterbuese, Ralf;
Junghahn, Ilse;
Kasimir-Bauer, Sabine;
Wimberger, Pauline;
Kimmig, Rainer;
Baeuerle, Patrick A.
Erschienen:
American Association for Cancer Research (AACR), 2005
Erschienen in:
Cancer Research, 65 (2005) 7, Seite 2882-2889
Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Bispecific T-cell engager (BiTE) are a class of bispecific single-chain antibodies that can very effectively redirect cytotoxic T cells for killing of tumor target cells. Here, we have assessed the in vivo efficacy of one representative, called bscEp-CAMxCD3, with specificity for tumors overexpressing epithelial cell adhesion molecule (Ep-CAM) in human xenograft models. Cells of the human colon carcinoma line SW480 were mixed at a 1:1 ratio with unstimulated human peripheral mononuclear cells, s.c. injected in nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mice, and animals were treated with bscEp-CAMxCD3. Five daily i.v. injections of as little as 100 ng per mouse of bscEp-CAMxCD3 completely prevented tumor outgrowth when treatment was started at the day of tumor cell inoculation. BscEp-CAMxCD3 was also efficacious when administered up to 8 days after xenograft injection. Established tumors could be eradicated in all animals by five 10 μg doses given between days 8 and 12 after tumor cell inoculation. To test the efficacy of bscEp-CAMxCD3 in a more physiologic model, pieces of primary metastatic tumor tissue from ovarian cancer patients were implanted in NOD/SCID mice. Partial tumor engraftment and growth was observed with four of six patient samples. Treatment of established tumors with daily 5 μg doses led to a significant reduction and, in some cases, eradication of human tumor tissue. These effects obviously relied on the tumor-resident T cells reactivated by bscEp-CAMxCD3. Our data show that the class of single-chain bispecific antibodies has very high antitumor efficacy in vivo and can use previously unstimulated T cells at low effector-to-target ratios.</jats:p>