In 1995, DTP implemented a new way to test the activity of potential anticancer compounds using cells grown inside biocompatible hollow fibers. The hollow fiber assay, developed by Dr. Melinda Hollingshead, chief of DTP’s Biological Testing Branch, has the ability to provide quantitative indices of drug efficacy in heterogeneous tumors with minimal expenditures of time and materials. This system currently is being used as the initial in vivo experience for agents found to have reproducible activity in the in vitro anticancer drug screen.
The hollow fiber assay has several advantages over standard animal efficacy models. First, demonstrating that potential anticancer agents have in vivo efficacy in one or more animal models of neoplastic disease can require considerable investments in laboratory animals and quantity of test compound. Second, conducting studies in animal models requires substantial amounts of time and resources. Even when such studies can be conducted, it is possible that the experimental agent or series of agents will exhibit only minimal antitumor activity. Third, cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proliferative and microenvironment heterogeneity that develops in these tumors as they grow.
The hollow fiber assay at full capacity allows screening of 50 or more compounds per 10-day assay. In addition to requiring less than two weeks to complete, the assay requires at most only 450 mg of material, as opposed to the multigram quantities required for many xenograft studies. Compounds that retard the growth of the selected tumor cell lines are recommended for the next level of testing.