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This article is part of the supplement: Abstracts of the 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

Open Access Poster presentation

Antitumor efficacy of D2C7-(scdsFv)-PE38KDEL, a novel immunotoxin targeting EGFRwt and EGFRvIII, by convection-enhanced delivery in orthotopic brain tumor mouse models

Xuhui Bao12*, Vidyalakshmi Chandramohan1, Stephen T Keir1, Charles N Pegram1, Roger E McLendon1, Chien-Tsun Kuan1, Ira H Pastan3 and Darell D Bigner1

  • * Corresponding author: Xuhui Bao

Author Affiliations

1 Pathology, Preston Robert Tisch Brain Tumor Center, Durham, NC, USA

2 Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

3 Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

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Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P126  doi:10.1186/2051-1426-1-S1-P126


The electronic version of this article is the complete one and can be found online at: http://www.immunotherapyofcancer.org/content/1/S1/P126


Published:7 November 2013

© 2013 Bao et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective

The epidermal growth factor receptor (EGFR) gene is most frequently amplified and overexpressed, along with its truncated mutant, EGFRvIII, in glioblastomas. We tested the antitumor efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL (D2C7-IT), which is reactive with a 55-amino acid (AA) region present in the extracellular domain of both EGFRwt and EGFRvIII proteins (Figure 1), by convection-enhanced delivery (CED) in orthotopic brain tumor mouse models established with human glioblastoma xenograft cells.

thumbnailFigure 1. Kaplan-Meier survival curves of different brain tumor models and the immunotoxin killing paradigm

Methods

Orthotopic brain tumor models were established by inoculating 43 (EGFRwt expressing glioma cell), D270MG (EGFRwt and EGFRvIII espressing glioma cells), and NR6M (EGFRvIII expressing fibroblast cells) intracranially in the immunocompromised mice. CED was achieved by inserting a cannula into the brain tumor site, which in turn was connected to a subcutaneous osmotic pump delivering the immunotoxin into the tumor microenvironment. The antitumor efficacy was evaluated by Kaplan-Meier survival analysis.

Results

In the orthotopic brain tumor models of 43, NR6M, and D270MG, D2C7-IT therapy via CED significantly prolonged the median survival time (MST) of the treatment group by about 1 month (P=0.0010), 1 week (P=0.0074), and over 1 month (P=0.0061), respectively, compared with that of vehicle or negative control groups (Table 1, Figure 1).

Table 1. Comparison of MST among different groups in three xenograft mouse models

Conclusion

In the orthotopic brain tumor mouse models, the D2C7-IT therapy via CED exhibited a robust therapeutic potential in treating brain tumors expressing EGFRwt, EGFRvIII, and both EGFRwt and EGFRvIII.