Anadys Pharmaceuticals presented data from an in vitro study showing that the active metabolite of ANA773 promotes natural killer (NK) cell-mediated anti-tumor response by inducing cytokine secretion, cytolysis of tumor cells and enhanced antibody-dependent cellular cytotoxicity (ADCC), during a poster presentation at the Annual Meeting of the American Association of Cancer Research (AACR) in Los Angeles.
The study found that the active metabolite of ANA773, an oral Toll-like receptor 7 (TLR7) agonist prodrug, induced the secretion of interferon-alpha (IFN-alpha) and various other cytokines from human peripheral blood mononuclear cells (PBMC) cultured in vitro. Human PBMC stimulated with the active metabolite of ANA773 increased NK cell cytotoxicity and cytokine secretion against both K562 erythroleukemic cells and transformed B cell lines. These in vitro effects were reduced by neutralization of IFN-alpha, confirming the role of cytokines induced by the TLR7 agonist in the killing of tumor cells.
In addition to enhancing direct NK cell killing of tumor cells, ANA773's active metabolite also enhanced ADCC. In this process, a specific antibody is used to identify tumor cells, which allows killer cells to target them for killing. This study showed that transformed B cells, targeted by addition of the anti-CD20 antibody rituximab, were killed more efficiently when PBMC containing the killer cells were treated with the active metabolite of ANA773.
"These data further support our belief that TLR7 is an attractive therapeutic target for the treatment of cancer," said Lawrence C. Fritz, Ph.D., president and chief executive officer of Anadys Pharmaceuticals. "We are excited about the possibility of combining ANA773, our next oral TLR7 prodrug agonist, with therapeutic antibodies against both B-cell malignancies and solid tumors. We plan to file an Investigational New Drug application for ANA773 in the second half of 2007."
Background
This study investigated the immunomodulatory effects of a low-molecular weight TLR7 agonist on human natural killer (NK) cell activity.