A single treatment of yttrium-90-labeled CHX-A″-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice

Gregory P. Adams, Calvin C. Shaller, Ekaterina Dadachova, Heidi H. Simmons, Eva M. Horak, Abohawariat Tesfaye, Andres J P Klein-Szanto, James D. Marks, Martin W. Brechbiel, Louis M. Weiner

Research output: Contribution to journalArticle

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Abstract

Antitumor diabody molecules are noncovalent single-chain Fv dimers that recapitulate the divalent binding properties of native IgG antibodies. Diabodies are capable of substantial accumulation in tumor xenografts expressing relevant antigens in immunodeficient mouse models. With a Mr of approximately 55,000, diabodies are rapidly cleared from the circulation, resulting in tumor-to-blood ratios that significantly exceed those achieved early after the administration of monoclonal antibodies. We have evaluated the therapeutic potential of the β-emitting isotope yttrium-90 (t1/2, 64 hours) conjugated to the C6.5K-A diabody that specifically targets the HER2/neu human tumor-associated antigen. We have found that a single intravenous dose of 150 μCi (200 μg) 90Y-CHX-A″C6.5K-A diabody substantially inhibits the growth rates of established MDA-361/ DYT2 human breast tumor xenografts in athymic nude mice. In contrast, 300 μCi (300 μg) 90Y-CHX-A″-C6.5K-A diabody resulted in only a minor delay in the growth of SK-OV-3 human ovarian cancer xenografts. The maximum tolerated dose was also dependent on the tumor xenograft model used. These studies indicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for radioimmunotherapy.

Original languageEnglish (US)
Pages (from-to)6200-6206
Number of pages7
JournalCancer Research
Volume64
Issue number17
DOIs
StatePublished - Sep 1 2004

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Yttrium
Heterografts
Growth
Yttrium Isotopes
Nude Mice
Neoplasms
Radioimmunotherapy
Single-Chain Antibodies
Maximum Tolerated Dose
Neoplasm Antigens
Therapeutics
Ovarian Neoplasms
Immunoglobulin G
Monoclonal Antibodies
Breast Neoplasms
Antigens
N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Adams, G. P., Shaller, C. C., Dadachova, E., Simmons, H. H., Horak, E. M., Tesfaye, A., ... Weiner, L. M. (2004). A single treatment of yttrium-90-labeled CHX-A″-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice. Cancer Research, 64(17), 6200-6206. https://doi.org/10.1158/0008-5472.CAN-03-2382

A single treatment of yttrium-90-labeled CHX-A″-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice. / Adams, Gregory P.; Shaller, Calvin C.; Dadachova, Ekaterina; Simmons, Heidi H.; Horak, Eva M.; Tesfaye, Abohawariat; Klein-Szanto, Andres J P; Marks, James D.; Brechbiel, Martin W.; Weiner, Louis M.

In: Cancer Research, Vol. 64, No. 17, 01.09.2004, p. 6200-6206.

Research output: Contribution to journalArticle

Adams, GP, Shaller, CC, Dadachova, E, Simmons, HH, Horak, EM, Tesfaye, A, Klein-Szanto, AJP, Marks, JD, Brechbiel, MW & Weiner, LM 2004, 'A single treatment of yttrium-90-labeled CHX-A″-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice', Cancer Research, vol. 64, no. 17, pp. 6200-6206. https://doi.org/10.1158/0008-5472.CAN-03-2382
Adams, Gregory P. ; Shaller, Calvin C. ; Dadachova, Ekaterina ; Simmons, Heidi H. ; Horak, Eva M. ; Tesfaye, Abohawariat ; Klein-Szanto, Andres J P ; Marks, James D. ; Brechbiel, Martin W. ; Weiner, Louis M. / A single treatment of yttrium-90-labeled CHX-A″-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice. In: Cancer Research. 2004 ; Vol. 64, No. 17. pp. 6200-6206.
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