Cleveland BioLabs, Inc. has announced that it has accumulated preclinical data demonstrating that CBLB502, a drug under development to treat exposure to radiation, has direct anticancer effect in several transplanted cancer models grown in mice and rats including colon and lung cancer, lymphoma and melanoma. In one of the animal models of transplanted colon cancer, CBLB502 treatment resulted in complete tumor regression with no recurrence of the disease in a large percentage of animals.
Experimental results suggest that CBLB502's anticancer effect stems from the same mechanism which underlies its ability to treat radiation exposure and which involves tissue-specific activation of innate immune response mediated by CBLB502's interaction with its receptor, TLR5. Antitumor effects largely depend on the expression of TLR5 by the tumor.
However, in the case of tumors residing in the liver, the organ which has been identified as the natural primary target site for CBLB502 activity, tumors become effectively suppressed as a result of host immune system attack regardless of their TLR5 status. This characteristic makes liver metastasis a favorable target for potential anticancer applications of CBLB502.
Andrei Gudkov, Ph.D., D. Sc., Chief Scientific Officer of Cleveland BioLabs and Senior Vice President of Basic Science at Roswell Park Cancer Institute, commented, "We are very excited by these initial results, which extend CBLB502's potential medical applications in cancer treatment from use as a supportive care agent to reduce toxicities of radio and chemotherapy to use as a direct anticancer agent. We believe that clinical development of CBLB502's potential immunotherapy effects may be pursued in parallel to or in some cases as part of, our prior plan for supportive care applications, and we are currently modifying our development plan to integrate this important new opportunity. We expect to complete these adjustments shortly and move forward into the clinic."
William Cance, M.D., Surgeon-in-Chief and Chair of the Department of Surgical Oncology at Roswell Park Cancer Institute, stated, "I have always thought that CBLB502 had the potential to revolutionize several areas of clinical cancer treatment through its ability to protect normal tissues. With this recent demonstration of direct anticancer activity, I believe the potential for CBLB502 to achieve broad clinical application becomes even more likely. I am especially excited about the observations regarding CBLB502's effect on tumors in the liver, as this property could make a significant difference in a currently hopeless category of patients with advanced liver metastasis."
These findings were the result of research into the tissue specific activity of CBLB502, which was funded by a Grand Opportunities (GO) grant under the American Recovery and Reinvestment Act of 2009 from the Office of the Director and the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).
This direction of research follows previous preclinical demonstrations of CBLB502's specific protection of normal tissues versus tumors, and its ability to protect such tissues in animal models of fractioned, localized radiation mimicking clinical regimens.