TLR5 Genetic Variants May Predict Antitumor Responses to Entolimod

BUFFALO, N.Y. — Roswell Park Comprehensive Cancer Center researchers examined the characteristics of genetic variants in human toll-like receptor 5 (TLR5), and have found that these genetic variants may predict antitumor responses to entolimod, an immunotherapeutic agent with antitumor activity. TLR5 plays a critical role in early immune response and is expressed in a wide variety of tumors and in normal tissues at common sites of metastases (eg, liver, lung). The results were presented at the American Association for Cancer Research Annual Meeting 2015, being held April 18-22 in Philadelphia.

Andrzej Wierzbicki, PhD, a postdoctoral fellow at Roswell Park, along with Araba Adjei, PhD, Associate Professor of Oncology in the Department of Pharmacology and Therapeutics at Roswell Park, and colleagues conducted the study “Functional characterization of human toll-like receptor 5 (TLR5) genetic variants” (abstract 5492). Alex Adjei, MD, PhD, Senior Vice President for Clinical Research at Roswell Park, also is a co-author of this study.

“This study suggests that genetic variations in TLR5, the target of entolimod, could predict how patients will respond to treatment, in terms of tumor shrinkage and development of potential side effects to the drug,” says Dr. Araba Adjei. “A recently completed phase 1 clinical study will further analyze the effect of these variations on toxicity and response to entolimod.”

Bacterial flagellin is the ligand recognized by TLR5. Flagellin binding to TLR5 results in the activation of multiple downstream signaling events. Naturally occurring variations of the TLR5 gene have been associated with immune disorders and diseases. Researchers evaluated the effect of nine of these variants in response to entolimod, a recombinant pharmacologically optimized form of Salmonella flagellin.

A wide range of variations in TLR5 protein levels was observed, along with corresponding ranges in activity, suggesting the possibility for variations in anticancer activities when patients demonstrating these TLR5 variants are treated with entolimod, according to Dr. Araba Adjei. Overall, the findings indicate that genetic variations in TLR5 may predict responses to treatment with entolimod.

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The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter.