Tse Wen Chang (, born August 25, 1947) is an immunology researcher, whose career spans across academia and industry. His early research involving the
Immunoglobulin E
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (Īµ chain) and two light chains, with the Ī ...
(IgE) pathway and
antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
-based therapeutics lead to the development of
omalizumab
Omalizumab, sold under the brand name Xolair, is a medication used to treat asthma, nasal polyps, and urticaria (hives).
Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglo ...
(also known as
Xolair
Omalizumab, sold under the brand name Xolair, is a medication used to treat asthma, nasal polyps, and urticaria (hives).
Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglo ...
), a medication that has been approved for the treatment of severe allergic
asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
and severe chronic spontaneous
urticaria
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...
. Chang is a cofounder of
Tanox
Tanox was a biopharmaceutical company based in Houston, Texas. The company was founded by two biomedical research scientists, Nancy T. Chang and Tse Wen Chang in March 1986 with $250,000, which was a large part of their family savings at that ...
, a biopharmaceutical company specialized in anti-
IgE
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (Īµ chain) and two light chains, with the Īµ c ...
therapies for the treatment of allergic diseases. After Tanox's tripartite partnership with
Genentech and
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
was forged in 1996, Chang returned to his alma mater, the
National Tsing Hua University
National Tsing Hua University (NTHU; ) is a public research university in Hsinchu City, Taiwan.
National Tsing Hua University was first founded in Beijing. After the Chinese Civil War, the then-president of the university, Mei Yiqi, and othe ...
in Taiwan and served as the Dean (1996ā1999) of the College of Life Sciences. Chang was appointed by the Taiwanese government as President of the Development Center for Biotechnology (DCB) in 2000, and served as a
Science and Technology Advisor of the
Executive Yuan from 2002 to 2006. From 2006 to 2016, he was tenured as Distinguished Research Fellow at the Genomics Research Center,
Academia Sinica. He founded Immunwork, Inc. in 2014.
Education
Chang was born and raised in
Zhongli District
Zhongli District () is a district in Taoyuan City, Taiwan. Zhongli is spelled variously as ''Jungli'', ''Jongli'', ''Jhongli'' or ''Chungli'' on railway stations, bus stops and road signs. Historically, the city is the site of the Zhongli Inciden ...
,
Taoyuan County
Taoyuan County () is under the administration of Changde, Hunan Province, China. The Yuan River, a tributary of the Yangtze, flows through Taoyuan. It covers an area of 4441 square kilometers, of which is arable land. It is from Zhangjiang To ...
, Taiwan in 1947. His ancestry traces back to
Mei County,
Guangdong Province, China. His father Chang Chun-an (å¼µåå®) spent his entire career working for the
Taiwan Railroad Bureau. Chang's mother, Yeh Ting-mei (čäø妹), was an elementary school teacher, who worked as a housewife after marriage to raise five children. Chang obtained a bachelor's degree (1970) and master's degree (1972) in chemistry at the
National Tsing Hua University
National Tsing Hua University (NTHU; ) is a public research university in Hsinchu City, Taiwan.
National Tsing Hua University was first founded in Beijing. After the Chinese Civil War, the then-president of the university, Mei Yiqi, and othe ...
. Afterwards, Chang received a four-year fellowship at
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of high ...
, where he did thesis research on
protein degradation
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
in the muscle during fasting with
Alfred L. Goldberg. Chang received his Ph.D. in 1977, and did postdoctoral research on
T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
immune mechanisms with
Herman Eisen at the Center for Cancer Research at
MIT
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the m ...
from 1977 to 1980.
Career
Contributions to biomedicine
Chang invented anti-
IgE
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (Īµ chain) and two light chains, with the Īµ c ...
therapeutics in 1987. IgE plays a central role in the initiation of hypersensitivity reactions in the human body, and is responsible for allergic diseases that affect 20ā40% of the population in developed countries. Originating from Chang's research, antibodies that target the IgE-mediated allergic pathway have proven effective in the treatment of various allergic diseases. Among these anti-IgE drugs are: Omalizumab (Xolair), approved by the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) for the treatment of allergic asthma and chronic spontaneous urticaria (primarily an autoimmune disease);
Talizumab (TNX-901), shown to be effective in treating
allergic rhinitis
Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...
(hay fever) and
peanut allergy
Peanut allergy is a type of food allergy to peanuts. It is different from tree nut allergies, because peanuts are legumes and not true nuts. Physical symptoms of allergic reaction can include itchiness, hives, swelling, eczema, sneezing, as ...
; and
Ligelizumab, a high-affinity TNX-901 under active clinical development at
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
.
In 1993, Chang's patent was granted for his discovery of CĪµmX, a unique region on human membrane-bound IgE (mIgE), leading to another therapeutic approach to treating IgE-mediated diseases.
Apart from anti-IgE therapeutics, Chang also first proposed the concept and methodology of the
antibody matrix
An antibody microarray (also known as antibody array) is a specific form of protein microarray. In this technology, a collection of captured antibodies are spotted and fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and ...
in 1983. By aligning antibodies of distinct specificities in a matrix-like manner, scientists are able to detect and quantify multiple
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
s in one simultaneous attempt. Thereafter, many other types of microarrays emerged, including
DNA microarrays and
protein microarray
A protein microarray (or protein chip) is a high-throughput method used to track the interactions and activities of proteins, and to determine their function, and determining function on a large scale. Its main advantage lies in the fact that larg ...
s, among others.
Work in biotechnology
In March 1986, Tse Wen and
Nancy T. Chang founded
Tanox
Tanox was a biopharmaceutical company based in Houston, Texas. The company was founded by two biomedical research scientists, Nancy T. Chang and Tse Wen Chang in March 1986 with $250,000, which was a large part of their family savings at that ...
, Inc., where he served as Vice President of Research & Development (1986ā1996) and director of the board from 1986 until Tanox was acquired by Genentech in 2007. In order to secure funding for a start-up company based on family funds, the Changs sought collaboration with
Genentech in 1989, sending data and samples of early anti-IgE antibody, but talks with Genentech were unsuccessful.
In 1990, Tanox partnered with
Ciba-Geigy
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loca ...
(which later merged with
Sandoz
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loca ...
to form
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
) and started developing
Talizumab (TNX-901).
A few years later, legal disputes arose as the Changs discovered that Genentech launched its own anti-IgE program, developing what now became known as
Omalizumab
Omalizumab, sold under the brand name Xolair, is a medication used to treat asthma, nasal polyps, and urticaria (hives).
Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglo ...
(Xolair). The Changs took it to the court in 1993 and accused Genentech of misappropriating its work, but the legal battle dragged on. Chang was granted patents in 1995. In 1996, Tanox and Genentech settled out of court, with Genentech paying Tanox a compensation. The two companies and Novartis agreed to jointly develop Xolair, under the reasoning that Genentech had better manufacturing processes to produce antibodies in large quantities. Chang not only proposed the theory behind anti-IgE therapeutics, but also actively participated in the phase I and II
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...
s of Talizumab from 1990 to 1996.
Meanwhile, after the settlement in 1996, Tanox continued to develop Talizumab, not for allergic asthma but for peanut allergy. In 2001ā2003, Talizumab entered
phase II clinical trials
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
for peanut allergy, and obtained very positive results.
Genentech, however, sued Tanox, arguing that their contract in 1996 should prevent Tanox from developing any potential competitor drugs to Xolair. Again, the dispute rose to the court. Although Tanox won the consent in a
federal district court
The United States district courts are the trial courts of the U.S. federal judiciary. There is one district court for each federal judicial district, which each cover one U.S. state or, in some cases, a portion of a state. Each district cou ...
, it lost the arbitration that followed, and the development of Talizumab for peanut allergy was suspended.
Post-Tanox
In 2014, Chang started the company Immunwork in Taiwan.
Investing attempts
Chang tried his hand at investing, purchasing large quantities of derivatives under Deutsche Bank's advice. Unfortunately, his scientific expertise did not translate into financial acumen, and as a result he lost $50 million in total. Chang initiated a counter-claim for the amount lost in response to the bank's claim for a sum of $1.7 million. While successful in his claim at the High Court, the decision was reversed on appeal, where the Singapore Court of Appeal stated that he had the requisite knowledge of shares to not rely on the advice of the bank. He also had to repay a $1.7 million debt incurred from investment losses. This case has since become a point of authority in contract law.
Awards and honors
* Honorary Fellow Award from the
American College of Allergy, Asthma, and Immunology (ACAAI), 2004.
*
Nature Biotechnology
''Nature Biotechnology'' is a monthly peer-reviewed scientific journal published by Nature Portfolio. The chief editor heads an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial busi ...
's shortlist of personalities who made the most significant contribution to biotech in the past 10 years.
* Honorary Fellow Award from
American Academy of Allergy, Asthma, and Immunology
Founded in 1943, the American Academy of Allergy, Asthma & Immunology (AAAAI) is a professional medical membership organization of nearly 6,800 allergist/ immunologists and related professionals around the world with advanced training and experie ...
(AAAAI), 2007.
*
The World Academy of Sciences
The World Academy of Sciences (TWAS) is a merit-based science academy established for developing countries, uniting 1,000 scientists in some 70 countries. Its principal aim is to promote scientific capacity and excellence for sustainable deve ...
(TWAS)
Prize
A prize is an award to be given to a person or a group of people (such as sporting teams and organizations) to recognize and reward their actions and achievements. in Medical Sciences, 2014.
Selected publications
* Chang TW, Tang N, 1972,
Selection pressure of homologous proteins of varied activities"
''Nature'', 239, 207.
* Chang TW, Kung PC, Gingras SP, and Goldstein G, 1981,
Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells? ''
Proc. Natl. Acad. Sci. USA'', 78, 1805ā1808.
* Chang TW, Kato I, McKinney S, Chanda P, Barone AD, Wong-Staal F, Gallo RC, and Chang NT, 1985,
Detection of antibodies to human T-cell lymphotropic virus-III (HTLV-III) with an immunoassay employing a recombinant Escherichia coli-derived viral antigenic peptide" ''
Nature Biotechnology
''Nature Biotechnology'' is a monthly peer-reviewed scientific journal published by Nature Portfolio. The chief editor heads an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial busi ...
'', 3, 905ā909.
* Chang TW, Davis FM, Sun NC, Sun CRY, MacGlashan Jr. DW, and Hamilton RG, 1990,
Monoclonal antibodies specific for human IgE-producing B cells: a potential therapeutic for IgE-medicated allergic diseases" ''
Nature Biotechnology
''Nature Biotechnology'' is a monthly peer-reviewed scientific journal published by Nature Portfolio. The chief editor heads an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial busi ...
'', 8, 122ā126.
* Peng C, Davis FM, Sun LK, Liou RS, Kim Y-W, and Chang TW, 1992,
A new isoform of human membrane-bound IgE" ''
Journal of Immunology
The ''Journal of Immunology'' is a biweekly peer-reviewed medical journal that publishes basic and clinical studies in all aspects of immunology. Established in 1916, it changed its name to ''Journal of Immunology, Virus Research and Experimental C ...
'', 148, 129ā136.
* Chang TW, 2000,
The pharmacological basis of anti-IgE therapy" ''
Nature Biotechnology
''Nature Biotechnology'' is a monthly peer-reviewed scientific journal published by Nature Portfolio. The chief editor heads an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial busi ...
'', 18(2), 157ā162.
* Chang TW and Shiung YY, 2006,
Anti-IgE as a mast cell-stabilizing therapeutic agent" ''
The Journal of Allergy and Clinical Immunology
''The Journal of Allergy and Clinical Immunology'' is a monthly peer-reviewed medical journal covering research on allergy and immunology. It is one of two official journals of the American Academy of Allergy, Asthma, and Immunology. The journal ...
'', 117(6), 1203ā1212.
* Chang TW, Wu PC, Hsu CL, Hung AF, 2007,
Anti-IgE antibodies for the treatment of IgE-mediated allergic diseases" ''Advances in Immunology'', 93, 63ā119.
* Chang TW and Pan AY, 2008,
Cumulative environmental changes, skewed antigen exposure, and the increase of allergy" ''Advances in Immunology'', 98, 39ā83.
* Chen JB, Wu PC, Hung AF, Chu CY, Tsai TF, Yu HM,
Chang HY, Chang TW, 2010,
Unique epitopes on C epsilon mX in IgE-B cell receptors are potentially applicable for targeting IgE-committed B cells" ''
Journal of Immunology
The ''Journal of Immunology'' is a biweekly peer-reviewed medical journal that publishes basic and clinical studies in all aspects of immunology. Established in 1916, it changed its name to ''Journal of Immunology, Virus Research and Experimental C ...
'', 184(4), 1748ā1756.
* Chu HM, Wright J, Chan YH, Lin CJ, Chang TW & Lim C, 2014,
Two potential therapeutic antibodies bind to a peptide segment of membrane-bound IgE in different conformations" ''
Nature Communications
''Nature Communications'' is a peer-reviewed, open access, scientific journal published by Nature Portfolio since 2010. It is a multidisciplinary journal and it covers the natural sciences, including physics, chemistry, earth sciences, medici ...
'', 5, 3139.
* Chang TW, Chen C, Lin CJ, Metz M, Church MK, Maurer M, 2015,
The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria" ''
The Journal of Allergy and Clinical Immunology
''The Journal of Allergy and Clinical Immunology'' is a monthly peer-reviewed medical journal covering research on allergy and immunology. It is one of two official journals of the American Academy of Allergy, Asthma, and Immunology. The journal ...
'', 135(2), 337ā342.e2.
References
External links
*
Immunwork, Biotech company founded and directed by Chang.
{{DEFAULTSORT:Chang, Tse Wen
1947 births
Taiwanese immunologists
National Tsing Hua University alumni
Taiwanese biotechnologists
Living people
Harvard University alumni
People from Taoyuan City
TWAS laureates
Taiwanese expatriates in the United States