Combination Therapy Shows Potent Tumor Growth Inhibition in Preclinical Studies
- VEGF and Ang2 are critical factors required for tumor angiogenesis.
- Combined blockade of VEGF and Ang2 with investigational agents enhances antitumor activity in preclinical studies.
- Combination of REGN910 with aflibercept warrants further clinical investigation.
SAN FRANCISCO — Combining the investigational agents REGN910 and aflibercept yielded statistically significant improvements in antitumor effects in animal models compared with either agent alone, according to results presented at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011.
“These preclinical findings suggest that combining REGN910 (SAR307746) and aflibercept in the clinic could be an attractive approach for future clinical research,” said Alshad S. Lalani, Ph.D., director of strategic oncology development at Regeneron Pharmaceuticals Inc. in Tarrytown, N.Y. “The rationale is that inhibition of tumor angiogenesis by combining antiangiogenesis treatments could translate into more potent and durable antitumor responses than those observed with single-agent therapy.”
In this preclinical mouse study, researchers from Regeneron and BC Cancer Agency in Vancouver, British Columbia, Canada, monitored how REGN910 and aflibercept blocked vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2), which are critical growth factors for tumor angiogenesis, or blood vessel formation.
REGN910 is a fully human monoclonal antibody discovered using Regeneron VelocImmune antibody technology that binds and inhibits Ang2. Aflibercept is a fully human fusion protein that binds all forms of VEGF-A, as well as VEGF-B and placental growth factor. REGN910 and aflibercept are being developed by Regeneron and Sanofi.
In addition, researchers performed tissue analyses to monitor the number of tumor blood vessels, tumor hypoxia (oxygen deprivation), tumor cell death and tumor perfusion.
“When used alone in animal studies, both REGN910 and aflibercept blocked tumor angiogenesis and growth; however, the combination of the two led to increased tumor hypoxia and consequently to the death of a large percentage of the tumor cells,” Lalani said. “Consistent with its ability to promote rapid and widespread tumor cell death in histology, the combination treatment inhibited tumor growth to a significantly greater extent than the single agents in multiple tumor models — colorectal, mammary and prostate. In particular, it caused dramatic tumor regression in the colorectal tumor models. Importantly, no visible evidence of toxicities or enhanced body weight loss was observed following the combination treatment.”
In ongoing animal studies, Lalani and colleagues are studying the reasons behind the results with the combined therapy. They are also investigating biomarkers that will allow them to monitor the combination therapy treatment effect and/or to identify which tumors are most likely to respond to treatment.
Follow the AACR on Facebook: http://www.facebook.com/aacr.org
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 laboratory, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards to young investigators, and it also funds cutting-edge research projects conducted by senior researchers. The AACR has numerous fruitful collaborations with organizations and foundations in the U.S. and abroad, and functions as the Scientific Partner of Stand Up To Cancer, a charitable initiative that supports groundbreaking research aimed at getting new cancer treatments to patients in an accelerated time frame. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care, and Educational Workshops are held for the training of young cancer investigators. The AACR publishes seven major peer-reviewed journals: Cancer Discovery; Cancer Research; Clinical Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Prevention Research. In 2010, AACR journals received 20 percent of the total number of citations given to oncology journals. The AACR also publishes Cancer Today, a magazine for cancer patients, survivors and their caregivers, which provides practical knowledge and new hope for cancer survivors. A major goal of the AACR is to educate the general public and policymakers about the value of cancer research in improving public health, the vital importance of increases in sustained funding for cancer research and biomedical science, and the need for national policies that foster innovation and the acceleration of progress against the 200 diseases we call cancer.
In San Francisco, Nov. 12-16: