Letter to the Editor: Fusion antibody Fc-endostatin

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TO THE EDITOR: We are interested in the article by Grossman et al.1 (Grossman R, Tyler B, Hwang L, et al: Improvement in the standard treatment for experimental glioma by fusing antibody Fc domain to endostatin. Laboratory investigation. J Neurosurg 115:1139–1146, December 2011).

Gliomas are highly angiogenic2,6 and refractory to conventional therapies.2–6 Studies on novel combination therapies are urgently needed. Grossman et al.1 performed a laboratory investigation to explore the effect of endostatin fused to antibody Fc domain (Fc-endostatin; mFc-endostatin for use in rodents) in combination with oral temozolomide (TMZ) on survival in a 9L gliosarcoma rat model. Their study demonstrated that either locally or systemically administered mFc-endostatin extended the survival of rats bearing orthotopic intracranial 9L gliosarcoma. Although the blood-brain barrier (BBB) is thought to restrict the delivery of drugs to gliomas, mFc-endostatin could exert its antiangiogenic effect against gliosarcoma even without passing through the BBB.

There are 2 flaws in their article. Firstly, in the Discussion, they stated that rats treated with mFc-endostatin did not show any remarkable local toxicity. In the Conclusions, they declared that the combination of subcutaneous mFc-endostatin with oral TMZ did not cause additional toxicity. Actually, the adverse effects of TMZ have been well documented, including nausea and vomiting.7 Theoretically, weight loss is a basic measurement of toxicity in an in vivo experiment. However, no experimental approach to assess in vitro or in vivo toxicity was addressed in the Methods of their article. Conclusions should be based on logical analyses of results obtained through adequate design of experimental methods. Secondly, in the Methods, control rats did not receive any treatment. This kind of study control is not stringent enough. Since Fc-endostatin has been modified through the fusion of endostatin to an antibody (IgG) Fc domain to overcome some deficiencies of bare endostatin, a better treatment control would be Fc-IgG control or denatured Fc-endostatin.

Despite these minor concerns, the authors' study provided important evidence of improved survival in gliosarcoma. For future translational research into humans, further studies are warranted to improve gliosarcoma outcomes.

References

  • 1

    Grossman RTyler BHwang LZadnik PLal BJavaherian K: Improvement in the standard treatment for experimental glioma by fusing antibody Fc domain to endostatin. Laboratory investigation. J Neurosurg 115:113911462011

  • 2

    Hueng DYLin GJHuang SHLiu LWJu DTChen YW: Inhibition of Nodal suppresses angiogenesis and growth of human gliomas. J Neurooncol 104:21312011

  • 3

    Jan HJLee CCShih YLHueng DYMa HILai JH: Osteopontin regulates human glioma cell invasiveness and tumor growth in mice. Neuro Oncol 12:58702010

  • 4

    Lee CCJan HJLai JHMa HIHueng DYLee YC: Nodal promotes growth and invasion in human gliomas. Oncogene 29:311031232010

  • 5

    Ma HIChiou SHHueng DYTai LKHuang PIKao CL: Celecoxib and radioresistant glioblastoma-derived CD133+ cells: improvement in radiotherapeutic effects. Laboratory investigation. J Neurosurg 114:6516622011

  • 6

    Ma HIGuo PLi JLin SZChiang YHXiao X: Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin. Cancer Res 62:7567632002

  • 7

    Rozzi ANardoni CCorona MRestuccia MRFabi ABria E: Palonosetron for the prevention of chemotherapyinduced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study. Support Care Cancer 19:6977012011

Response

No response was received from the authors of the original article.

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Article Information

DISCLOSURE The authors report no conflict of interest.

INCLUDE WHEN CITING Published online February 27, 2015; DOI: 10.3171/2012.2.JNS111886.

© AANS, except where prohibited by US copyright law.

Headings

References

  • 1

    Grossman RTyler BHwang LZadnik PLal BJavaherian K: Improvement in the standard treatment for experimental glioma by fusing antibody Fc domain to endostatin. Laboratory investigation. J Neurosurg 115:113911462011

  • 2

    Hueng DYLin GJHuang SHLiu LWJu DTChen YW: Inhibition of Nodal suppresses angiogenesis and growth of human gliomas. J Neurooncol 104:21312011

  • 3

    Jan HJLee CCShih YLHueng DYMa HILai JH: Osteopontin regulates human glioma cell invasiveness and tumor growth in mice. Neuro Oncol 12:58702010

  • 4

    Lee CCJan HJLai JHMa HIHueng DYLee YC: Nodal promotes growth and invasion in human gliomas. Oncogene 29:311031232010

  • 5

    Ma HIChiou SHHueng DYTai LKHuang PIKao CL: Celecoxib and radioresistant glioblastoma-derived CD133+ cells: improvement in radiotherapeutic effects. Laboratory investigation. J Neurosurg 114:6516622011

  • 6

    Ma HIGuo PLi JLin SZChiang YHXiao X: Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin. Cancer Res 62:7567632002

  • 7

    Rozzi ANardoni CCorona MRestuccia MRFabi ABria E: Palonosetron for the prevention of chemotherapyinduced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study. Support Care Cancer 19:6977012011

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