Marc Feldmann

Last updated

Sir

Marc Feldmann

AC
Born (1944-12-02) 2 December 1944 (age 78)
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, AC FAA FRS FRCP FRCPath FMedSci (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 2003, the Albert Lasker Award for Clinical Medical Research; [15] in 2002, the Cameron Prize for Therapeutics of the University of Edinburgh; 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]

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. [18]

In 2012 he delivered the Croonian Lecture to the Royal College of Physicians on anti-cytokine therapy. [19]

Related Research Articles

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">Tumor necrosis factor</span> Protein

Tumor necrosis factor is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.

<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> Pharmaceutical drug

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 N. 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">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.

Biological response modifiers (BRMs) are substances that modify immune responses. They can be both endogenous and exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.

<span class="mw-page-title-main">Lymphotoxin alpha</span> Protein found in humans

Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene. Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.

<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.

<span class="mw-page-title-main">Autoimmune inner ear disease</span> Medical condition

Autoimmune inner ear disease (AIED) was first defined by Dr. Brian McCabe in a landmark paper describing an autoimmune loss of hearing. The disease results in progressive sensorineural hearing loss (SNHL) that acts bilaterally and asymmetrically, and sometimes affects an individual's vestibular system. AIED is used to describe any disorder in which the inner ear is damaged as a result of an autoimmune response. Some examples of autoimmune disorders that have presented with AIED are Cogan's syndrome, relapsing polychondritis, systemic lupus erythematosus, granulomatosis with polyangiitis, polyarteritis nodosa, Sjogren's syndrome, and Lyme disease.

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.

Martin Turner is a molecular biologist and Head of the Lymphocyte Signalling & Development Laboratory at the Babraham Institute. His work has helped identify key molecular processes involved in the development of the immune system and its response to pathogens. His work has included research the fundamental mechanisms regulating gene expression by cells of the immune system.

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>

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.

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. ↑ "No. 59446". The London Gazette (Supplement). 12 June 2010. p. 1.
  19. ↑ "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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