Skip to Main Content

Abstract Details

AbstractDetails

Abstract Date: 5/2/2015

Author(s):
Frederick F. Lang, Jr., MD
Charles Conrad, MD
Candelaria Gomez-Manzano, MD
Frank Tufaro, PhD
Raymond Sawaya, MD
Jeffrey Weinberg, MD
Sujit Prabhu, MD
Gregory Fuller, MD, PhD
Kenneth Aldape, MD
Juan Fueyo, MD (Houston, TX)

Introduction
Delta-24-RGD is a novel replication-competent, tumor-selective, oncolytic adenovirus with enhanced infectivity. Based on promising preclinical studies, we undertook a first-in-human Phase I clinical trial with biological endpoints in order to assess the capacity of Delta-24-RGD to replicate in human gliomas, and to determine safety and initial efficacy.


Methods
Patients with recurrent high-grade gliomas were enrolled in one of two arms. Group A (clinical assessment group) received a single intratumoral injection of Delta-24-RGD into biopsy-proven recurrent glioma. Group B (biological endpoint group) received an initial intratumoral injection through an implanted catheter followed 14 days later by en bloc tumor/catheter resection (to obtain post-treatment specimens) and subsequent injection of Delta-24-RGD into the post-resection cavity. Dose was escalated in 8 cohorts (1x107-3x1010 vp).


Results
Histological analysis of post-treatment en bloc surgical specimens proved for the first time that Delta-24-RGD is capable of infecting, replicating in, and killing glioma tumor cells (Group B; N=12). Delta-24-RGD resulted in no toxicity and the MTD was 3×1010vp (Group A; N=25). Outcome analyses show an overall median survival of 11 months. Remarkably, complete responses were seen in 3 patients (12%) all of whom are alive (3.5, 2.5 and 2 years after treatment). Serial MRIs revealed increased enhancement before tumor regression, consistent with inflammatory mediated responses. Histological analysis of resected tumor from a symptomatic patient in Arm A during the period of increased MRI-enhancement identified macrophages and CD8 T-cells, but only rare tumor cells. Compared with all other patients, the 3-responders had 10-fold to 10000-fold increases in Interleukin-12p70 (which induces Th1-responses and cell-mediated immunity).

Conclusion: Delta-24-RGD is a new oncolytic virus with a favorable toxicity-profile that is capable of replicating in and killing human glioma cells, and that can produce durable complete-responses in subsets of patients. Viral-induced anti-tumor-immunity plays a role in the anti-glioma effect.

Keywords:

Article ID: AA-31555


Abstract Center

Support the NREF When You Shop

Register with iGive.com or AmazonSmile and designate the NREF as your charity.

Support the NREF

Donate Here