Antibody fragments fused to IL-12 and to TNF-alpha exert anti-tumor effect.

2003 SEP 3 - (NewsRx.com & NewsRx.net) -- The combination of a tumor-targeting antibody fragment fused to interleukin 12 and to tumor necrosis factor alpha exerts a synergistic effect against tumors.

"The potent antitumor activity of certain cytokines is often achieved at the expense of unacceptable toxicity. One avenue to improve the therapeutic index of cytokines in cancer therapy consists of fusing them to monoclonal antibodies capable of a selective localization at the tumor site. We have constructed fusion proteins of interleukin-12 (IL-12) and tumor necrosis factor (TNF-alpha) with L19, an antibody fragment specific to the extradomain B of fibronectin which has been shown to target tumors in animal models and in patients with cancer," scientists in Switzerland, Italy, and Germany report.

"These fusions display a potent antitumor activity in several immunocompetent murine models of cancer but do not lead to complete remissions of established aggressive tumors," stated Cornelia Halin at the Swiss Federal Institute of Technology in Zurich and collaborators in Switzerland, Germany, and Italy. "In this article, we have evaluated the tumor-targeting properties band the anticancer activities of combinations of the two antibody-cytokine fusion proteins, as well as of a triple fusion protein between IL-12, L19, and TNF-alpha."

The researchers reported, "Although all fusion proteins were active in vitro, the triple fusion protein failed to localize to tumors in vivo and to show significant therapeutic effects. By contrast, the combination of IL-12-L19 and L19-TNF-alpha displayed potent synergistic anticancer activity and led to the eradication of F9 teratocarcinomas grafted in immunocompetent ...