The results of our study should be of potential clinical interest. They provide a rational for the combination of TNF��, BAb, and RT in the treatment of adenocarcinoma of the pancreas. One of the advantages of our BAb strategy, namely, the potential decrease of TNF�� systemic toxicity, cannot be addressed in our nude mice model, www.selleckchem.com/products/Lenalidomide.html which lacks T cells. The difference between the TNF�� +RT and the BAb+TNF��+RT combination treatments will probably be even more evident in an immunocompetent model or in a clinical setting. Such an immunocompetent situation is also needed for the entire expression of TNF�� antitumour action, including immunological (production of IL-1 and IFN��, activation of macrophages, and NK cells; Dinarello et al, 1986; Ostensen et al, 1987; Talmadge et al, 1987) and nonimmunological mechanisms such as damage to the tumour vasculature (Gamble et al, 1985; Sato et al, 1986; Cavender et al, 1987; Ruegg et al, 1998).

In conclusion, we demonstrated that an anti-CEA/anti-TNF�� BAb can markedly enhance the radioresponse of pancreatic tumour xenografts in nude mice. Presently, we are testing the antitumour effect of BAb, TNF��, and RT combination in an immunocompetent CEA-transgenic mice transplanted with a syngenic CEA-expressing tumour in which all the effects of the targeted cytokine can be analysed. The next step will be the opening of a phase I clinical study in locally advanced pancreatic cancer. Acknowledgments This study was supported by the comit�� de l’H��rault de la Ligue Nationale Contre le Cancer. David Azria was supported by the Association de Recherche sur le Cancer.

We thank Genevieve Heinz, Sabine Bousqui��, Celine Passet, and Philippe Gauthier for excellent technical assistance; Michel Brissac for help in performing animal experiments; Dr Jacques Dornand for the TNF�� cytotoxicity assays; and Dr SL Salhi for critical comments and excellent editorial assistance. This work was presented in part at the Second International Conference of Translational Research and Preclinical Strategies in Radio-oncology, 16�C19 March 2003 in Lugano, Switzerland.
Liver-directed gene transfer is being investigated for the treatment of systemic or liver-specific diseases. Recombinant vectors based on adeno-associated virus serotype 8 (AAV2/8) efficiently transduce liver cells allowing long term transgene expression after a single administration in animal models and in patients. We evaluated the impact Batimastat on AAV2/8-mediated rat liver transduction of the following variables: i) age at vector administration, ii) presence of lysosomal storage in liver cells, and iii) regulatory elements included in the transgene expression cassette.