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Dec 08 News Vol 15 No 3 Final.Qxp ISICR Officers President Eleanor Fish President-elect Leonidas Platanias Secretary Tom Hamilton December 2008 - Volume 15, No. 3 Treasurer Bob Friedman Executive Director One on one: An Interview with Cliff Brownstein Giorgio Trinchieri, Recipient of the 2008 Milstein Award Future ISICR Meetings Thomas Tan 2009 Meeting Giorgio Trinchieri received his medical degree Joint ISICR/ICS/SLB from the University of Torino, Italy, in 1973. He Lisbon, Portugal was a member of the Basel Institute for Immunology (Basel, Switzerland) and an investi- 2010 Meeting gator at the Swiss Institute for Experimental Joint ISICR/ICS Cancer Research (Epalanges sur Lausanne, Chicago, Illinois Switzerland). From 1979 to 1999 he was at Wistar Institute in Philadelphia and became Hilary Koprowski Professor and Chairman of the Immunology Program; he ISICR WWW Site was also Wistar Professor of Medicine at the University of www.ISICR.org Pennsylvania. He then served as director of the Schering Plough Laboratory for Immunological Research in Dardilly, France, and an ISICR Business Office NIH Fogarty Scholar at the Laboratory for Parasitic Diseases, [email protected] NIAID, before becoming director of the Cancer and Inflammation TEL: 301-634-7250 Program (CIP) and Chief of the Laboratory of Experimental FAX: 301-634-7420 Immunology at NCI in August 2006. As CIP director, he oversees the operations of two major NCI intramural laboratories, the Laboratory ISICR Newsletter Editors of Experimental Immunology and the Laboratory of Molecular Howard Young Immunoregulation. These two laboratories constitute the major [email protected] immunologic component of the inflammation and cancer initiative, Fax: 301-846-1673 which spans the NCI's campuses in Frederick and Bethesda and seeks Hannah Nguyen to partner NCI's expertise in inflammation and immunology with its cutting-edge cancer etiology and carcinogenesis program. He has Seng-Lai (Thomas) Tan been interested for many years in the interplay between inflamma- [email protected] tion/innate resistance and adaptive immunity, and in the role of pro- inflammatory cytokines and interferons in the regulation of hematopoiesis, innate resistance and immunity. In 1989, his group at the Wistar Institute discovered Interleukin-12 (IL-12), and he has spent many years characterizing the molecular mechanisms of IL-12 production and action, and the role of this molecule in tumor immu- (continued on page 2) December, 2008 (Giorgio Trinchieri, cont. from page 1) 2. What disease indications do you think would best benefit from therapies targeting IL-12? immunity, infections and autoimmunity. His main focus of research is now the role of inflammation, As for many cytokines, the road to the clinical use of innate resistance, and immunity in carcinogenesis, IL-12 has been rocky with several sad failures in the cancer progression, and prevention or destruction of early clinical trials. Presently, most pharmaceutical cancer. companies that have acquired the rights for IL-12 have abandoned the development of IL-12 as a drug Questions: after many disappointing attempts in cancer therapy, 1. Congratulations on receiving this year's Milstein HIV, HCV, and vaccination for infectious diseases. Award. How did you become involved in IL-12 Still, a NCI appointed panel have recently identified research? IL-12 as one of the top three most promising biolog- ics for cancer therapy and NCI is coordinating fur- In 1985, my laboratory at the Wistar Institute had ther trials in cancer therapy of IL-12 as a single just identified that the so-called Differentiation agent therapy or in combination with other agents, Inducing Factor, which was able to induce differenti- e.g. IL-2. IL-12 still offers a potential usefulness as ation of immature myeloid cells as well as activation vaccine adjuvant, not only in cancer vaccines but of monocyte/macrophages and neutrophils, was not a also in vaccines for infectious diseases, both prophy- single factor but rather the combination of different lactic and therapeutic, due to its potent activity as an cytokines, particularly IFN gamma as well as tumor inducer of IFN-gamma production and of Th1 necrosis factor and lymphotoxin. In order to continue responses, as well as its ability to favor the genera- these studies, we decided to purify lymphotoxin to tion of memory and effector cytotoxic T cells. But homogeneity from the supernatant of a human EBV- most promising, rather than the use of IL-12 as a transformed cell line, RPMI 7788, that was produc- drug, is the therapeutic use of IL-12 antagonists, par- ing large amounts of this cytokine. In a separate line ticularly monoclonal antibodies. IL-12 plays an of research, we were using in the laboratory the same important role in autoimmunity as an inducer of Th1 cell line as a potent stimulus for the expansion of responses but it was more recently discovered that human Natural Killer (NK) cells and we had identi- the potent ability of anti-IL-12 antibodies to reverse fied that the supernatant of that cell lines contained a many experimental models of autoimmune diseases factor that we called NK cell stimulatory factor was due to the ability of the antibodies to neutralize (NKSF), able to enhance NK cell cytotoxic activity not only IL-12 but also IL-23, a cytokine sharing the and to induce IFN-gamma production from NK cells. p40 chain with IL-12 and important for endowing NKSF was different from the two factors that we the recently discovered Th17 cells with pathogenic have previously discovered to be potent NK cell acti- activity. Antibodies against IL-12 p40 (thus neutral- vators, type I IFN and IL-2. Thus, when a senior izing both IL-12 and IL-23) have been found to be post-doc in my laboratory, Dr. Michiko Kobayashi, dramatically effective in clinical trials against psoria- started the purification of lymphotoxin, I decided to sis and colitis and have a potential to replace anti- test the fractions for NKSF activity. The first gel fil- TNF antagonists as first line therapy in these and tration fractionation did not separate lymphotoxin possibly other autoimmune diseases. from NKSF but a subsequent MonoQ fractionation clearly showed that the two activities were due to 3. Who was your mentor or role model in your distinct proteins. It was only because of Michiko’s scientific career? technical ability and perseverance that NKSF/IL-12 was then purified to homogeneity, shown to be the In a scientific career that it is now more than 40 first described heterodimeric cytokine, and the two years, I have been in contact with many investiga- chains sequenced. Then, with the instrumental help tors, colleagues, and friends who have deeply affect- of Dr. Stan Wolf at Genetics Institute, the two genes ed my vision and approach to science. Mentors have encoding IL-12 were cloned. been important but I do not believe in role models, rather I think it is the daily interaction with every- 2 International Society for Interferon and Cytokine Research (Giorgio Trinchieri, cont. from page 2) ing explorations as before but still a lot of fun and one of the occasions to spend as much of my free body in the laboratory as well as collaborators that time as possible with my family. shape us as scientists and thinkers. The relationship with collaborators, postdoctoral fellows, students, 6. Torino is famous for many things: Fiat (Fabbrica and technicians is really two-way and I think one Italiana Automobili Torino), Juventus FC (the great learns from each of them as much or more than one Italian soccer team), and Lavazza (Italy's largest cof- gives to them. I treasure all those personal interac- fee roaster). What do you miss the most about Italy tions more than any scientific accomplishment or in general now that you're living in success in my career. When I was a young medical Frederick/Bethesda? student and Prof. Ruggero Ceppellini in 1967 asked I moved from Italy in 1970 but I still like to go me to volunteer as a student in his Institute of back there for vacation every year. I enjoy the Medical Genetics in Turin, it was like he was reading culture, the history as well as the food and the wine. the dreams in my mind. Ruggero taught me to be But my entire scientific career was outside Italy and enthusiastic for scientific discovery, always keeping I found the challenging and competitive scientific in mind the medical applications of my work and he environment in the U.S. the most stimulating I have gave me a strong interest in human genetics that experienced. never left me even when the focus of my work was far from genetics. When I moved to Basel Dr. Niels 7. What are some of the main differences between Jerne taught me to recognize the forest from the trees the Schering-Plough Laboratory for Immunological and that ideas, not technologies, should drive the sci- Research in France, DNAX and NCI in terms of entific quest. At the Wistar Institute, Dr. Hilary their respective research environment and culture? Koprowski taught me how it is important to recog- nize that similar immunopathogenetic mechanisms Through the years I have experienced many different are involved in viral and bacterial infections, cancer, research environments in different countries: univer- and autoimmunity and the enthusiasm for interdisci- sities, independent or company-supported research plinary and translational research that I learned from institutes, and intramural NIH centers. To be honest, him has deeply influenced my scientific work. More I mostly miss the academic environment, the interac- recently my dear friend Dr. Alan Sher has tried to tion with students is always very stimulating and the make a parasitologist out of me; it was tempting and continuous search for grants and funding might be he almost but not quite succeeded, it is not easy to stressful but really makes one feel that only one’s teach new tricks to an old dog.
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