Marc Feldmann

Last updated

Professor
Sir Marc Feldmann
AC FRS FAA FRCP FRCPath FMedSci
Born (1944-12-02) 2 December 1944 (age 79)
Lvov
CitizenshipAustralia/United Kingdom
Alma mater
Known fordiscovery of anti-TNF therapy for rheumatoid arthritis and other autoimmune diseases
Awards
Scientific career
Fields Immunology
Institutions
Doctoral students Ashok Venkitaraman [1]

Sir Marc Feldmann (born 2 December 1944) is an Australian-educated British immunologist. He is a professor at the University of Oxford and a senior research fellow at Somerville College, Oxford. [2]

Contents

Biography

Feldmann was born 2 December 1944 in Lvov to a Jewish family who managed to get to France immediately postwar. [3] [4] [5] He emigrated from France to Australia at age eight. [5] After graduating with an MBBS degree from the University of Melbourne in 1967, he earned a Ph.D. in Immunology at the Walter and Eliza Hall Institute of Medical Research in 1972 with Sir Gustav Nossal. [3] [4]

He moved to London in the 1970s, working first with Avrion Mitchison at the Imperial Cancer Research Fund's Tumour Immunology Unit; in 1985 he moved to the Charing Cross Sunley Research Centre and the Kennedy Institute of Rheumatology (which joined with the Faculty of Medicine at Imperial College in 2000; in August 2011 the Institute transferred to the University of Oxford. [4]

Research

In the 1980s he published an hypothesis for the mechanism of induction of autoimmune diseases, highlighting the role of cytokines. [6] This model was validated in experiments with thyroid disease tissue. From 1984 he collaborated with Ravinder N. Maini at the Kennedy Institute of Rheumatology to study disease mechanism in rheumatoid arthritis, an autoimmune disease affecting 1% of the population. [7]

Feldmann's group demonstrated that diseased joints have far more pro-inflammatory cytokines than normal, and postdoctoral researcher Fionula Brennan identified one of these, tumour necrosis factor alpha, (abbreviated TNFα) as the key. [8]

Blocking TNFα reduced levels of the other pro-inflammatory cytokines in test-tube models of arthritis, [9] and this provided the rationale for testing TNF blockade in rheumatoid arthritis patients which had failed all existing treatment.

The first of a series of successful clinical trials was performed in 1992 at Charing Cross Hospital, using the antibody infliximab from Centocor, a biotech now part of Johnson and Johnson.[ citation needed ]

The success led to other companies joining the race to market. By 1998, [10] etanercept (Enbrel) [11] was approved for treatment in the US, and by 1999, infliximab (Remicade) was also approved; there have been multiple additional approved anti-TNF drugs, and they have become standard therapy for stopping the inflammatory and tissue-destructive pathways of rheumatoid arthritis and other autoimmune diseases including Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriasis and psoriatic arthritis. [7] [12]

Prizes and fellowships

In 2000, Feldmann and Maini were awarded the Crafoord Prize; [13] [14] in 2002, the Cameron Prize for Therapeutics of the University of Edinburgh; in 2003, the Albert Lasker Award for Clinical Medical Research; [15] in 2008, the Dr. Paul Janssen Award for Biomedical Research; [16] in 2010, the Ernst Schering Prize in Germany; in 2014, the Canada Gairdner International Award. Feldmann was also awarded the John Curtin Medal of the Australian National University in 2007. In 2020 he received the Tang Prize in Biopharmaceutical Science. [17] and in 2024 the Royal Medal of the Royal Society jointly with Ravinder N. Maini. [18]

Feldmann is Fellow of the Royal College of Physicians and of the Royal College of Pathologists. He was elected a Fellow of several national Academies, the Academy of Medical Sciences, the Royal Society of London and is a Corresponding Member of Australian Academy of Science, and a Foreign Member of the National Academy of Sciences, US. He was knighted in the 2010 Queen's Birthday Honours. [19]

In 2012 he delivered the Croonian Lecture to the Royal College of Physicians on anti-cytokine therapy. [20]

Related Research Articles

<span class="mw-page-title-main">Rheumatoid arthritis</span> Type of autoimmune arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

<span class="mw-page-title-main">Infliximab</span> Biopharmaceutical drug for autoimmune disorders

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Tumor necrosis factor alpha (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.

<span class="mw-page-title-main">Ravinder Maini</span>

Sir Ravinder Nath Maini is an Indian-born British rheumatologist and academic who is an emeritus professor at Imperial College London. He led the Kennedy Institute of Rheumatology.

<span class="mw-page-title-main">Tadamitsu Kishimoto</span> Japanese immunologist (born 1939)

Tadamitsu Kishimoto is a Japanese immunologist known for research on IgM and cytokines, most famously, interleukin 6.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

<span class="mw-page-title-main">Certolizumab pegol</span> Pharmaceutical drug

Certolizumab pegol, sold under the brand name Cimzia, is a biopharmaceutical medication for the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. It is a fragment of a monoclonal antibody specific to tumor necrosis factor alpha (TNF-α) and is manufactured by UCB.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

<span class="mw-page-title-main">Jan Vilček</span> Slovak immunologist (born 1933)

Jan T. Vilček is a Slovak-American biomedical scientist, educator, inventor and philanthropist. He is a professor in the department of microbiology at the New York University School of Medicine, and chairman and CEO of The Vilcek Foundation. Vilček received his M.D. degree from Comenius University Medical School in Bratislava in 1957; and his Ph.D. in Virology from the Institute of Virology, Czechoslovak Academy of Sciences, Bratislava, in 1962.

<span class="mw-page-title-main">Anti–citrullinated protein antibody</span> Autoantibodies

Anti-citrullinated protein antibodies (ACPAs) are autoantibodies that are directed against peptides and proteins that are citrullinated. They are present in the majority of patients with rheumatoid arthritis. Clinically, cyclic citrullinated peptides (CCP) are frequently used to detect these antibodies in patient serum or plasma.

The Dr. Paul Janssen Award for Biomedical Research is given annually by Johnson & Johnson to honor the work of an active scientist in academia, industry or a scientific institute in the field of biomedical research. It was established in 2004 and perpetuates the memory of Paul Janssen, the founder of Janssen Pharmaceutica, a Johnson & Johnson subsidiary.

Detection of autoantibodies against mutated citrullinated vimentin is part of rheumatoid arthritis (RA) diagnostics, especially in sera negative for rheumatoid factor. Anti-MCV antibodies are a member of the ACPA family, a group of the so-called antibodies to citrullinated protein/peptide antigens.

Anti-interleukin-6 agents are a class of therapeutics. Interleukin 6 is a cytokine relevant to many inflammatory diseases and many cancers. Hence, anti-IL6 agents have been sought. In rheumatoid arthritis they can help patients unresponsive to TNF inhibitors.

Olokizumab (OKZ) sold under the name Artlegia, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis and COVID-19. It is a humanized monoclonal antibody against the interleukin-6 (IL-6). IL-6 is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases. Olokizumab is the first interleukin-6 (IL-6) inhibitor approved for treatment of rheumatoid arthritis which blocks directly cytokine instead of its receptor. Olokizumab specifically binds to IL-6 at Site 3, blocking IL-6 ability to form hexameric complex. Olokizumab was developed by R-Pharm group, and was launched in 2020.

Otilimab is a fully human antibody which has been developed by the biotechnology company MorphoSys. It can also be referred to as HuCAL antibody, HuCAL standing for Human Combinatorial Antibody Library and being a technology used to generate monoclonal antibodies. Otilimab is directed against the granulocyte-macrophage colony stimulating factor (GM-CSF), a monomeric glycoprotein functioning as a cytokine promoting both proliferation and activation of macrophages and neutrophils.

<span class="mw-page-title-main">Lars Klareskog</span> Biologist

Lars Klareskog is a Swedish physician, immunologist, and rheumatologist, known for research into the genetics of autoimmune diseases such as rheumatoid arthritis (RA).

Fionula Brennan (1957–2012) was an Irish immunologist and Professor of Cytokine Immunopathology at the Kennedy Institute of Rheumatology.

The Kennedy Trust for Rheumatology Research is a registered UK charity which funds the Kennedy Institute as well as a range of individual UK university-based researchers. Its longer-term objective is to "achieve a meaningful impact in the development of cures and preventative treatment for musculoskeletal and related inflammatory diseases".

References

  1. ↑ Venkitaraman, Ashok Ramakrishnan (1989). The regulation of MHC class 2 gene expression by tumours of the B lymphocyte lineage (PhD thesis). Imperial College London. hdl: 10044/1/47696 .
  2. ↑ "Sir Marc Feldmann". Somerville College, Oxford . Retrieved 1 April 2020.
  3. 1 2 Feldmann, M. (2009) Translating molecular insights in autoimmunity into effective therapy. Annu. Rev. Immunol. 27: 1-27.
  4. 1 2 3 "Feldmann, Marc". ISIHighlyCited.com. Retrieved 21 November 2008.
  5. 1 2 "Marc Feldmann" (PDF). Johnson & Johnson Pharmaceutical Services. Retrieved 21 November 2008.
  6. ↑ Bottazzo, G.F., Pujol-Borrell, R., Hanafusa, T. and Feldmann, M. (1983) Hypothesis: Role of aberrant HLA-DR expression and antigen presentation in the induction of endocrine autoimmunity. Lancet ii: 1115-1119.
  7. 1 2 "Professor Marc Feldmann wins top lifetime achievement award". News-Medical.Net. 24 April 2007. Retrieved 21 November 2008.
  8. ↑ Feldmann, M., Brennan, F.M. and Maini, R.N. (1996) Role of cytokines in rheumatoid arthritis. Annu Rev. Immunol. 14: 397-440.
  9. ↑ Brennan, F.M., Chantry, D., Jackson, A., Maini, R.N. and Feldmann, M. (1989) Inhibitory effect of TNF-alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet ii: 244-247.
  10. ↑ Elliott, M.J., Maini, R.N., Feldmann, M., Long-Fox, A., Charles, P., Katsikis, P., Brennan, F.M., Walker, J., Bijl, H., Ghrayeb, J. and Woody, J. (1993) Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to TNF-alpha. Arth. Rheum 36: 1681-90.
  11. ↑ Elliott, M.J., Maini, R.N., Feldmann, M., Kalden, J.R., Antoni, C., Smolen, J.S., Leeb, B., Breedveld, F.C., Macfarlane, J.D., Bijl, H. and Woody, J.N. (1994) Randomised double-blind comparison of a chimeric monoclonal antibody to tumour necrosis factor-alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344: 1105-1110.
  12. ↑ Feldmann, M. and Maini, R.N. (2001) Anti-TNF-alpha therapy of rheumatoid arthritis: What have we learned? Annual Review Immunology 19: 163-196.
  13. ↑ "Crafoord Prize 2000". The Royal Swedish Academy of Sciences . Retrieved 23 November 2008.[ dead link ]
  14. ↑ "Crafoord Prize 2000 Press Release". The Royal Swedish Academy of Sciences. Retrieved 24 November 2008.[ dead link ]
  15. ↑ "The 2003 Albert Lasker Clinical Medical Research Award". Lasker Foundation. Retrieved 21 November 2008.
  16. ↑ "Professors Marc Feldmann and Sir Ravinder Maini Named Winners of the 2008 Dr. Paul Janssen Award for Biomedical Research". Johnson & Johnson Pharmaceutical Services. Archived from the original on 29 January 2010. Retrieved 23 November 2008.
  17. ↑ Tang Prize 2020
  18. ↑ Royal Medal 2024
  19. ↑ "No. 59446". The London Gazette (Supplement). 12 June 2010. p. 1.
  20. ↑ "Royal College of Physicians- Events Diary". Royal College of Physicians. Archived from the original on 23 December 2012. Retrieved 7 September 2012.
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