E-Letter responses to:

special/viewpoint: Ralph M. Steinman and Ira Mellman Immunotherapy: Bewitched, Bothered, and Bewildered No More Science 2004; 305: 197-200 [Abstract] [Full text] [PDF]

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Published E-Letter responses:

Human Immunotherapy Research is Developing

Douglas J Veale, Ursula Fearon   (30 July 2004)

Human Immunotherapy Research is Developing 30 July 2004
Douglas J Veale, Clinician Scientist / Rheumatologist SVUH ERC & Conway Institute, Dublin, Ireland, Ursula Fearon Respond to this E-Letter: Re: Human Immunotherapy Research is Developing	The authors are to be congratulated for identifying and honestly confronting key issues, which for too long have remained the "nettle" so many have failed to grasp! A prominent example of "bewitched" immunotherapy was anti-CD4 therapy in the treatment of rheumatoid arthritis (RA) (1, 2). I would strongly agree with the authors assertion that "investigation in the clinic and the laboratory is a two-way street." I would suggest also that studies of cancer immunotherapy should inform us regarding autoimmune diseases and infection, and vice versa, as many basic mechanisms are similar. Our group studies matrix turnover and angiogenesis, which are good examples of overlap between such disciplines. The authors highlight "access to internal tissues or to use routine analytical methods" as a key bothersome issue. Recently however, our group have published novel examples of what is possible, if human tissue is obtained (3, 4). Synovial tissue explant culture systems ex vivo provide reproducible mechanistic and immunotherapeutic studies and can be coordinated with magnetic resonance imaging. Reports of autologous stem cell transplantation or immunotherapy may also provide valuable lessons regarding the "immunostat" (5, 6). In Dublin, currently, there is a research revolution that addresses some of the obstacles outlined by Steinman and Mellman. Key partnerships between government and funding bodies have established The Science Foundation of Ireland and The Conway Institute/The Dublin Molecular Medicine Centre with close links to St. Vincent’s University Hospital, where a new genome resource unit is under construction. This constellation of research resources espouses the principles of Steinman and Mellman and a major Immunotherapy initiative is underway. Dedicated, professional logistical and regulatory staff are key to the success of such an initiative. The authors bravely make the point regarding elite, basic science journals; however, this may have driven the development of increasingly reliable human model systems. I emphasize that human research would benefit from greater multidisciplinary involvement across the clinical specialty spectrum as well as the scientific. This is especially true for immunotherapy, for example, anti-TNF therapy appears to be effective in RA, Crohns disease, psoriasis, psoriatic arthritis, and other autoimmune diseases. In relation to funding, there is clearly an opportunity for partnership between clinical science and the Pharma industry, which should ultimately benefit the patients. Such partnerships however require mutual investment and absolute transparency. References: 1. Choy EH, Tucansa IC, Kinsgley GH, Corrigal V, Panayi GS. Treatment of RA with single dose or weekly pulses of chimeric anti CD4 monoclonal antibody. J Scan Immunol 1992 36(2);291-8. 2. Veale DJ, Reece RJ, Parsons W, Radjenovic A, O'Connor PJ, Orgles CS, Berry E, Ridgway JP, Mason U, Boylston AW, Gibbon W, Emery P. Intra- articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology. Ann Rheum Dis. 1999 Jun;58(6):342-9. 3. Fraser A, Fearon U, Reece R, Emery P, Veale DJ. Matrix Metalloproteinases, Apoptosis and Vascular Morphology in Early Arthritis. Arthritis Rheum 2001, 44(9);2024-8. 4. McEvoy AN, Bresnihan B, FitzGerald O, Murphy EP. Cyclooxygenase 2- derived prostaglandin E2 production by corticotropin-releasing hormaone contributes to the activated camp response element binding protein content in rheumatoid synovial tissue. Arthritis Rheum 2004 50(4):1132-45. 5. Bingham S, Veale D, Fearon U, Isaacs JD, Morgan G, Emery P, McGonagle D, Reece R, Clague R, Snowden JA. High-dose cyclophosphamide with stem cell rescue for severe rheumatoid arthritis: short-term efficacy correlates with reduction of macroscopic and histologic synovitis. Arthritis Rheum. 2002 Mar;46(3):837-9. 6. Conaghan PG, Sommer S, McGonagle D, Veale D, Waldmann H, Hale G, Goodfield M, Emery P, Isaacs J. The relationship between pityriasis rubra pilaris and inflammatory arthritis: case report and response of the arthritis to anti-tumor necrosis factor immunotherapy. Arthritis Rheum. 1999 Sep;42(9):1998-2001.