Thomas A Waldmann

Thomas A Waldmann (born 21 September 1930) is an American immunologist who has worked on therapeutic monoclonal antibodies to the IL-2 receptor, Interleukin 15 (IL-15), and Adult T-cell Leukemia (ATL). He is currently an active distinguished investigator at the Lymphoid Malignancies Branch of the National Cancer Institute.[1]

Thomas A Waldmann

Biography and career

Thomas Waldmann was born in New York City as the only child of Elisabeth Sipos and Charles Waldmann. He received his M.D. from Harvard Medical School in 1955. He joined the NCI in 1956 and became chief of the Lymphoid Malignancies Branch (formerly Metabolism Branch) in 1973. He married the late Katharine Waldmann in 1958 and has three Children: Richard, Robert, and Carol Waldmann.[2]

Research

Waldmann's research has focused on lymphokines, their receptors, and use of lymphokines and monoclonal antibodies to their receptors in the treatment of cancer and of autoimmune diseases. He studied the IL-2/IL-2 receptor system in the growth of normal and neoplastic cells. He co-discovered IL-15 and has initiated clinical trials employing IL-15 in the treatment of metastatic malignancy.

He studied the role played by the receptor for interleukin-2 (IL-2) on the growth, differentiation and regulation of normal and neoplastic T-cells. He defined the IL-2 receptor subunits IL-2R beta and IL-2R alpha using the first reported anticytokine monoclonal antibody (anti-Tac)[3] leading to the definition of the IL-2R alpha as a target for the therapy of leukemia and autoimmune diseases.

The scientific basis for this approach was the fact that normal resting cells do not express IL-2R alpha, but it is expressed by abnormal T-cells in patients with lymphoid malignancies. He introduced different forms of IL-2R-directed therapy, including unmodified murine antibodies to IL-2R alpha (anti-Tac, the first antibody to a cytokine receptor to receive FDA approval),[4] humanized anti-Tac (daclizumab, Zenapax) and the antibody armed with toxins or alpha and beta-emitting radionuclides.

He showed that daclizumab contributes to reducing renal transplant rejection and is of value in the treatment of T-cell-mediated autoimmune disorders including multiple sclerosis.[5]

He demonstrated that refractory and relapsed Hodgkin's lymphoma (HL) patients could be effectively treated with daclizumab armed with Yttrium-90, because most normal cells do not express CD25, but it is expressed by some Reed-Sternberg cells and by rosetting polyclonal T-cells in lymphomatous masses. Responses were seen among the patients whose Reed-Sternberg cells were CD25 negative, provided that the associated rosetting T-cells expressed CD25.[6][7]

Waldmann co-discovered the cytokine interleukin 15 (IL-15)[8][9] and elucidated its role in the development of NK and CD8-memory T cells and its inhibition of activation induced cell death. He demonstrated that it is bound to IL-15 R alpha on the surface of antigen presenting cells and presented in trans to T-cells in an immune synapse [10] He demonstrated that IL-15 is useful in the treatment of cancer in mice and has completed a clinical trial using IL-15 in therapy of patients with metastatic malignant melanoma and renal cell cancer.[11]

Furthermore, Waldmann demonstrated that vaccines containing IL-15 induced long-lasting, high-avidity CD8-mediated CTL immunity.[12][13]

Waldmann studied adult T-cell leukemia that develops in individuals infected with the retrovirus human T-cell lymphotropic virus-1 (HTLV-1). Dr. Waldmann demonstrated that the HTLV-1 encoded protein Tax constitutively activates two autocrine (IL-2R/IL-2, IL-15R/IL-15) and one paracrine (IL-9) system. Waldmann demonstrated that daclizumab provides effective therapy for some patients with a previously invariably fatal leukemia, HTLV-I associated adult T-cell leukemia (ATL).[14]

In the early 80s Waldmann studied immunoglobulin gene rearrangement in and cell surface markers on acute lymphocyte leukemias[15]

In 1961 Waldmann described Waldmann disease.

Honorary Societies
  • National Academy of Sciences, [16]
  • American Academy of Arts and Sciences,[17]
  • National Academy of Medicine,[18]
  • Fellow National Academy of Inventors,[19]
  • Association of American Physicians [20]
  • American Society for Clinical Investigation [21]
  • The Hungarian Academy of Sciences[22]
  • Fellow American Association for the Advancement of Sciences[23]
  • Fellow American Academy of Microbiology [24]
  • Honorary Life Membership of the International Cytokine Society[25]
  • Honorary Fellow Royal Society of the Medical Sciences (UK)[26]
  • Election to the Henry Kunkel Society[27]
  • Fellow American Physiological Society [28]
  • Honorary Member Clinical Immunology Society[29]

Awards[30]
  • 1974 Bela Schick Award, The American Academy of Allergy, Asthma & Immunology
  • 1977 Henry M Stratton Medal, the American Society of Hematology
  • 1980 G. Burroughs Mider Award, National Institutes of Health
  • 1980 Man of the Year, the Leukemia and Lumphoma Society
  • 1984 John M. Shelton Award, The American Academy of Allergy, Asthma & Immunology
  • 1986 Lila Gruber Cancer Research Award, American Academy of Dermatology[31]
  • 1987 Ciba-Geigy Drew Award in Biomedical Research,
  • 1987 Simon Shubitz Prize for Cancer Research, University of Chicago Medical School,
  • 1989 Milken Family Medical Foundation, Distinguished Basic Scientist Award,
  • 1990 Doctor Honoris Causa, University Medical School, Debrecen, Hungary,
  • 1991 Artois-Baillet Latour Health Prize,
  • 1992 15th Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research,
  • 1996 Paul Ehrlich Medal, Paul Ehrlich Institute,[32]
  • 1998 American College of Physicans Award for Distinguished Contributions to Science as Related to Medicine,[33]
  • 2002 American Academy of Microbiology-Abbott Laboratories Prize in Clinical Diagnostic Immunology,
  • 2005 Debrecen Prize in Molecular Medicine,
  • 2007 Dana Foundation Prize, American Association of Immunologists
  • 2007 AAI- Ralph Steinman Award for Human Immunology Research,[34]
  • 2007 Clinical Immunology Society Presidential Award [35]
  • 2009 Service to America (SAMMIE) Career Achievement Medal,[36]
  • 2011 Establishment of the Annual Thomas Waldmann Award Foundation for Primary Immunodeficiency Diseases (FPID),[37]
  • 2012 Institute of Human Virology Life-time Achievement Award,[38]
  • 2012 FLC Award for Excellence in Technology Transfer for use of Therapeutic Antibodies as a Novel Treatment for Multiple Sclerosis,[39]
  • 2018 Albert Nelson Marquis Lifetime Achievement Award[40]
  • 2007 President's Award Clinical Immunology Society[41]


References
  1. https://ccr.cancer.gov/Lymphoid-Malignancies-Branch/thomas-a-waldmann
  2. https://www.annualreviews.org/doi/abs/10.1146/annurev.immunol.21.120601.140933
  3. Uchiyama T, Broder S, Waldmann TA. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol 1981, 126(4):1393-7. PMID 6970774
  4. Waldmann TA, Goldman CK, Bongiovanni KF, Sharrow SO, Davey MP, Cease KB, Greenberg SJ, Longo DL. Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2. Blood 1988, 72(5): 1805-16. PMID 2846094
  5. Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, Frank JA, Würfe J, Ohayon J, Waldmann TA, McFarland HF, Martin R. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon-beta. Proc Natl Acad Sci USA 2004, 101(23)8705-8708. PMID 15161974
  6. Conlon KC, Sportes C, Brechbiel MW, Fowler DH, Gress R, Miljkovic MD, Chen CC, Whatley MA, Bryant BR, Corcoran EM, Kurdziel KA, Pittaluga S, Paik CH, Lee JH, Fleisher TA, Carrasquillo JA, Waldmann TA. 90Y-Daclizumab (Anti-CD25), High-Dose Carmustine, Etoposide, Cytarabine, and Melphalan Chemotherapy and Autologous Hematopoietic Stem Cell Transplant Yielded Sustained Complete Remissions in 4 Patients with Recurrent Hodgkin's Lymphoma. Cancer Biother Radiopharm. 2020
  7. Janik JE, Morris JC, O'Mahony D, Pittaluga S, Jaffe ES, Redon CE, Bonner WM, Brechbiel MW, Paik CH, Whatley M, Chen C, Lee-J-H, Fleisher TA, Brown M, White JD, Stewart DM, Fioravanti S, Lee CC, Goldman CK, Bryant BR, Junghans RP, Carrasquillo JA, Worthy TY, Corcoran E, Conlon KC, Waldmann TA. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma. Proc Natl Acad Sci USA, 2015, 112(42):13045-13050. PMID 26438866
  8. Burton JD, Bamford RN, Peters C, Grant AJ, Kurys G, Goldman CK, Brennan J, Roessler E, Waldmann TA. A lymphokine, provisionally designated interleukin-T, produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA 1994, 91(11):4935-9. PMID 8197160
  9. Bamford RN, Grant AJ, Burton JD, Peters C, Kurys G, Goldman CK, Brennan J, Roessler E, Waldmann TA. The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA 1994, 91(11):4940-44. PMID 8197161
  10. 197. Dubois S, Mariner J, Waldmann TA Tagaya Y. IL-15R alpha recycles and presents IL-15 in trans to neighboring cells. Immunity 2002, 17(5):537-547. PMID 12433361
  11. Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, Fleisher TA, Dubois SP, Perera LP, Stewart DM, Goldman CK, Bryant BR, Decker JM, Chen J, Worthy TYA, Figg WD, Sr, Peer CJ, Sneller MC, Lane HC, Yovandich JL, Creekmore SP, Roederer M, Waldmann TA. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015, 33(1):74-82. PMID 25403209
  12. Perera LP, Waldmann TA, Mosca JD, Baldwin N, Berzofsky JA, Oh SK. Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. J Virol. 2007, 81(16):8774-8783. PMID 17553867
  13. Poon LLM, Leung YHC, Nicholls JM, Perera P-Y, Lichy JH, Yamamoto M, Waldmann TA, Peiris JSM, Perera LP. Vaccinia virus-based multivalent H5N1 avian influenza vaccines adjuvanted with IL-15 confer sterile cross-clade protection in mice. J Immunol. 2009, 182(5):3063-3071. PMID 19234203
  14. Berkowitz JL, Janik JE, Stewart DM, Jaffe ES, Stetler-Stevenson M, Shih JH, Fleisher TA, Turner M, Urquhart NE, Wharfe GH, Figg WD, Peer CJ, Goldman CK, Waldmann TA, Morris JC. Safety, efficacy and pharmacokinetics/pharmacodynamics, of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma. Clin Immunol. 2014, 155(2):176-187. PMID 25267440
  15. Korsmeyer SJ, Arnold A, Bakhshi A, Ravetch JV, Siebenlist U, Hieter PA, Sharrow SO, LeBien TW, Kersey JH, Poplack DG, Leder P, Waldmann TA. Immunoglobulin gene rearrangement and cell surface antigen expression of acute lymphocyte leukemias of T-cell and B-cell precursor origins. J Clin Invest 1983, 71(2):301-13. PMID 6401769
  16. http://www.nasonline.org/member-directory/members/45743.html
  17. https://www.amacad.org/person/thomas-alexander-waldmann
  18. https://nam.edu/member/?member_id=BLt1yfVN%2FmHP91nmUKZ7kQ%3D%3D
  19. https://academyofinventors.org/wp/skin/search-fellows.php
  20. https://aap-online.org/admin/members.php?search=1&last_name=W
  21. https://www.the-asci.org/controllers/asci/AsciProfileController.php?pid=158321
  22. https://mta.hu/koztestuleti_tagok?PersonId=19580
  23. https://www.aaas.org/fellows/listing
  24. https://myasm.asm.org/eweb/DynamicPage.aspx?WebCode=directoryProfile&key=016e8050-fd5e-433d-91a7-38bb955addf8
  25. https://cytokinesociety.org/about-us/honorary-members/
  26. https://ccr.cancer.gov/Lymphoid-Malignancies-Branch/thomas-a-waldmann
  27. https://www.henrykunkelsociety.org/assets/docs/2015-final-kunkel-society-meeting-program.pdf
  28. https://www.physiology.org/community/aps-membership/aps-fellows/FAPS-Awardees?SSO=Y
  29. https://marquistopdoctors.com/2018/10/29/thomas-waldmann/
  30. https://wwlifetimeachievement.com/2018/09/08/thomas-waldmann/
  31. "Lila and Murray Gruber Memorial Cancer Research Award and Lectureship". www.aad.org. Retrieved 2021-02-03.
  32. https://www.aai.org/About/History/AAI-Awardees/ThomasAWaldmann
  33. https://www.acponline.org/system/files/documents/about_acp/awards_masterships/awards.pdf
  34. https://www.aai.org/About/History/AAI-Awardees/ThomasAWaldmann
  35. https://clinimmsoc.org/CIS/About/Awards.htm
  36. https://servicetoamericamedals.org/honorees/thomas-alexander-waldmann/
  37. https://fpid.org/wp/thomas-a-waldmann-award/
  38. https://www.aai.org/About/History/AAI-Awardees/ThomasAWaldmann
  39. https://federallabs.org/successes/awards/awards-gallery/2011/2011-use-of-therapeutic-antibodies-as-a-novel-treatment-for
  40. "Thomas Waldmann Presented with the Albert Nelson Marquis Lifetime Achievement Award by Marquis Who's Who". 24-7 Press Release Newswire. Retrieved 2021-02-03.
  41. "CIS - Awards". clinimmsoc.org. Retrieved 2021-02-03.
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