Abstract Details

Title Significance of Cancer Autoantibodies in Patients with Malignant Gliomas Treated with Delta-24-RGD

Topic Neuro-oncology

Presentation(s) S56 - (-)

Poster/Presentation
Number 001

Objective

Background Treatment of glioma xenografts with Delta-24-RGD oncolytic adenovirus resulted in the eradication of the tumor in more than 50% of the cases (Fueyo et al. 2003). These results were reproduced using a glioma stem cell model (Jiang et al 2007). Infection of glioma cells triggers autophagy (Jiang et al 2011) one of the main mechanisms responsible for antigen presentation in adenovirus infected cells.

Design/Methods Serum from patients enrolled in the clinical trial was collected before Delta-24-RGD administration (always) and then at several time points after the treatment. Autoantibodies were detected using a modified solid-phase ELISA. Titer of 30 autoantibodies was calculated. These included antibodies against: NY ESO1, MAGE, CTAG, CSAG, SSX families of antigens and autoantibodies against other cancer related proteins such as BRAF, SOX2 and p53. Antigen expression, when it was possible, was documented by immunohistochemistry staining of surgical sections of the tumors.

Results Patients that showed with high titer of autoantibodies against more than 16 antigens before the administration of Delta-24-RGD showed (at this moment of the trial) poorer clinical outcomes than those patients whose sera harbored autoantibodies against 15 or less antigens or did not show autoantibodies.

Conclusions These data are very preliminary, but strongly suggest that the existence of a humoral response against the glioma before the injection of Delta-24-RGD may preclude the development of an effective adenovirus-based anti-glioma immune response. We believe that our data may be of significance for the evaluation of results from clinical trials involving immunotherapy of brain tumors including those utilizing oncoytic viruses and glioma vaccines.

Authors/Disclosures
Juan Fueyo, MD, FAAN (U.T. M.D. Anderson Cancer Center) PRESENTER	No disclosure on file
Candelaria Gomez Manzano, MD, FAAN (MD Anderson Cancer Center)	No disclosure on file
Charles A. Conrad, MD (UT MD Anderson)	No disclosure on file
W K A. Yung, MD, FAAN (UT MD Anderson Cancer Center)	No disclosure on file
	No disclosure on file
	No disclosure on file
Peter J. McAllister, MD, FAAN (New England Inst for Neurology and Headache)	Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for lilly. Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for abbvie. Dr. McAllister has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for lundbeck.
	No disclosure on file

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