Combined treatment of the immunoconjugate bivatuzumab mertansine and fractionated irradiation improves local tumour control in vivo

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• 作者：Kristin Gurtner^a ; ^b ; Franziska Hessel^a ; ^b ; Wolfgang Eicheler^a ; ^b ; Annegret Dö ; rfler^a ; ^b ; Daniel Zips^a ; ^b ; Karl-Heinz Heider^c ; Mechthild Krause^a ; ^b ; ^{mechthild.krause@uniklinikum-dresden.de} ; Michael Baumann^a ; ^b
• 关键词：Combined treatment ; Molecular targeting ; Antibody ; Fractionated irradiation ; Local tumour control ; CD44v6 ; Bivatuzumab mertansine
• 刊名：Radiotherapy and Oncology
• 出版年：2012
• 期刊代码：231_01678140
• 类别：med
• 出版时间：March, 2012
• 卷：102
• 期：3
• 页码：444-449
• 文件大小：645 K

摘要

Background and purpose

To test whether BIWI 1 (bivatuzumab mertansine), an immunoconjugate of the humanized anti-CD44v6 monoclonal antibody BIWA 4 and the maytansinoid DM1, given simultaneously to fractionated irradiation improves local tumour control in vivo compared with irradiation alone.

Material and methods

For growth delay, FaDu tumours were treated with 5 intravenous injections (daily) of phosphate buffered saline (PBS, control), BIWA 4 (monoclonal antibody against CD44v6) or BIWI 1 (bivatuzumab mertansine) at two different dose levels (50 渭g/kg DM1 and 100 渭g/kg DM1). For local tumour control, FaDu tumours received fractionated irradiation (5f/5d) with simultaneous PBS, BIWA 4 or BIWI 1 (two dose levels).

Results

BIWI 1 significantly improved local tumour control after irradiation with 5 fractions already in the lower concentration. The dose modifying factor of 1.9 is substantial compared to the majority of other modifiers of radiation response.

Conclusion

Because of the magnitude of the curative effect, this approach is highly promising and should be further evaluated using similar combinations with improved tumour-specificity.