Ursula Wiedermann

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Ursula Wiedermann (born 5 August 1965) [1] is an Austrian medical scientist who has made significant contributions in the field of allergies and of cancer immunotherapy. She is currently Professor of Vaccinology at the Medical University of Vienna. Wiedermann's work in the field of B cell peptide vaccines led to the creation of HER-Vaxx, an immunotherapy for the treatment of HER-2-positive cancers. This vaccine is currently being taken into mid-stage clinical development in gastric cancer by the biotech company Imugene, where Wiedermann is Chief Scientific Officer.

Contents

Background

After obtaining an MD degree from the Medical University of Vienna, Wiedermann gained a PhD in Immunology at the University of Gothenburg in Sweden, where the focus of her PhD work was mucosal immunity and vaccination. After returning to the Medical University of Vienna Wiedermann researched mucosal vaccination against allergic diseases and later began to look at vaccine development against infectious diseases and tumours as well as explore the issues of immune responsiveness and immune failures upon vaccination. Wiedermann became head of Vienna's Institute of Specific Prophylaxis and Tropical Medicine in 2004 and was named Professor of Vaccinology in 2006. [2]

Allergy research

A theme of Wiedermann's allergy research has been the treatment of allergies via mucosal tolerance induction with recombinant allergens, [3] probiotics or other microbes. For a key 2001 paper in the International Archives of Allergy and Immunology Wiedermann used recombinant fragments of the birch pollen allergen Bet v I to induce mucosal tolerance in a mouse model of birch pollen allergy. [4] In 2008 the Wiedermann lab challenged the 'microflora hypothesis', which holds that altered microflora contributed to allergies, by showing that Bet v 1 could induce mucosal tolerance in mice regardless of the presence or absence of microflora. [5] In 2009 the Wiedermann lab provided some supporting evidence for the hygiene hypothesis of allergies by showing that infection with the intracellular parasite Toxoplasma gondii could prevent allergic immune responses in birch pollen allergic mice. [6] In 2011 the Wiedermann lab showed in mice that probiotics could have anti-allergic effects against multiple allergens. [7] In 2012 the Wiedermann lab showed that a fusion protein containing several allergens could treat birch pollen-related food allergy, in which patients are allergic to homologues of Bet v I. [8] Also in 2012 the Wiedermann lab showed in mice that perinatal administration of Lactobacillus paracasei to pregnant and lactating mothers could protect against the development of airway inflammation in offspring. [9]

Cancer immunotherapy research

Beginning around 2004 Wiedermann began to working on the technology that evolved into HER-Vaxx, a B cell peptide cancer immunotherapy that could induce an antibody response targeting HER-2 overexpressing tumours. Following on from favourable pre-clinical data, [10] Wiedermann et al. ran a small 10-patient safety study of HER-Vaxx in ten patients with Stage IV metastatic breast cancer, albeit with low HER-2 expression. This study found the vaccine to be safe, with no observed cardiotoxicity. The patients developed anti-HER-2 antibodies and in vitro, those anti-HER-2 antibodies showed potent anti-tumour activity. Also in vitro, blood from the patients carried markers of a cellular immune response such as IL-2, IFN-γ and TNF-α (meaning that ultimately patients could be expected to develop T cells to kill the cancer cells, and not just antibodies). The vaccine took down the ‘T reg’ cell count in the patients, potentially indicating an overcoming of the cancer’s immunoresistance. [11] In 2012 a start-up company called Biolife Science was incorporated to develop this immunotherapy. Early-stage funding was secured from Australian and US investors in 2013, after which Biolife was taken public in December 2013 in a reverse takeover of an Australian drug development company called Imugene, whose name was retained after the merger. Wiedermann joined Imugene's Scientific Advisory Board in January 2014 [12] and was named Chief Scientific Officer of Imugene in June 2015. [13]

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Allergy</span> Immune system response to a substance that most people tolerate well

Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions.

An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

<span class="mw-page-title-main">Ragweed</span> Genus of plants

Ragweeds are flowering plants in the genus Ambrosia in the aster family, Asteraceae. They are distributed in the tropical and subtropical regions of the Americas, especially North America, where the origin and center of diversity of the genus are in the southwestern United States and northwestern Mexico. Several species have been introduced to the Old World and some have naturalized and have become invasive species. Ragweed species are expected to continue spreading across Europe in the near future in response to ongoing climate change.

<span class="mw-page-title-main">Allergic rhinitis</span> Nasal inflammation due to allergens in the air

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, itchy, and watery eyes, and swelling around the eyes. The fluid from the nose is usually clear. Symptom onset is often within minutes following allergen exposure, and can affect sleep and the ability to work or study. Some people may develop symptoms only during specific times of the year, often as a result of pollen exposure. Many people with allergic rhinitis also have asthma, allergic conjunctivitis, or atopic dermatitis.

<span class="mw-page-title-main">Immunoglobulin E</span> Immunoglobulin E (IgE) Antibody

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

<span class="mw-page-title-main">Allergic conjunctivitis</span> Medical condition

Allergic conjunctivitis (AC) is inflammation of the conjunctiva due to allergy. Although allergens differ among patients, the most common cause is hay fever. Symptoms consist of redness, edema (swelling) of the conjunctiva, itching, and increased lacrimation. If this is combined with rhinitis, the condition is termed allergic rhinoconjunctivitis (ARC).

<span class="mw-page-title-main">Allergen immunotherapy</span> Medical treatment for environmental allergies

Allergen immunotherapy, also known as desensitization or hypo-sensitization, is a medical treatment for environmental allergies, such as insect bites, and asthma. Immunotherapy involves exposing people to larger and larger amounts of allergens in an attempt to change the immune system's response.

Oral allergy syndrome (OAS) or pollen-food allergy is a type of food allergy classified by a cluster of allergic reactions in the mouth and throat in response to eating certain fruits, nuts, and vegetables. It typically develops in adults with hay fever.

Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissues that would otherwise have the capacity to elicit an immune response in a given organism. It is induced by prior exposure to that specific antigen and contrasts with conventional immune-mediated elimination of foreign antigens. Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced—in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). The mechanisms by which these forms of tolerance are established are distinct, but the resulting effect is similar.

Allergies to cats are one of the most common allergies among human individuals. Among the eight known cat allergens, the most prominent allergen is secretoglobin Fel d 1, which is produced in the anal glands, salivary glands, and, mainly, in sebaceous glands of cats, and is ubiquitous in the United States, even in households without cats. The second most common is Fel d 2, this type is triggered by the cats dead skin flakes (dander) that are floating in the air as well as in the smell of cat urine.

<span class="mw-page-title-main">Egg allergy</span> Type of food allergy caused by eggs

Egg allergy is an immune hypersensitivity to proteins found in chicken eggs, and possibly goose, duck, or turkey eggs. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaphylaxis, a potentially life-threatening condition which requires treatment with epinephrine. Other presentations may include atopic dermatitis or inflammation of the esophagus.

ALK-Abelló A/S, also commonly known as ALK, is a Denmark-based pharmaceutical company which specializes in the development and manufacturing of allergy immunotherapy (AIT) products for the prevention and treatment of allergy. It is one of the world's largest makers of allergy immunotherapy products with 67% of its revenue coming from sales in Europe.

Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

Cross-reactive carbohydrate determinants (CCDs) play a role in the context of allergy diagnosis. The terms CCD or CCDs describe protein-linked carbohydrate structures responsible for the phenomenon of cross-reactivity of sera from allergic patients towards a wide range of allergens from plants and insects. In serum-based allergy diagnosis, antibodies of the IgE class directed against CCDs therefore give the impression of polysensitization. Anti-CCD IgE, however, does not seem to elicit clinical symptoms. Diagnostic results caused by CCDs are therefore regarded as false positives.

Imugene Ltd is a clinical stage immuno-oncology company developing a range of new and novel immunotherapies that seek to activate the immune system of cancer patients to treat and eradicate tumours. Imugene's unique platform technologies seeks to harness the body's immune system against tumours, potentially achieving a similar or greater effect than synthetically manufactured monoclonal antibody and other immunotherapies.

CRM197 is a non-toxic mutant of diphtheria toxin, currently used as a carrier protein for polysaccharides and haptens to make them immunogenic. There is some dispute about the toxicity of CRM197, with evidence that it is toxic to yeast cells and some mammalian cell lines.

<span class="mw-page-title-main">HAL Allergy Group</span>

HAL Allergy Group is a pharmaceutical company that develops, produces and sells products for allergy diagnostic and allergen immunotherapy (AIT). The research facilities and headquarters are located at the Leiden Bio Science Park, Netherlands.

References

  1. ↑ "Univ. Prof. Dr. Ursula WIEDERMANN, MD, MSc, PhD" (PDF). Medical University of Vienna Researcher Profiles. Retrieved 25 April 2022.
  2. ↑ "PhD Program, Molecular, Cellular and Clinical Allergology". Phd-mcca.at. Retrieved 3 December 2015.
  3. ↑ Wiedermann U. (October 1, 2005). "Prophylaxis and therapy of allergy by mucosal tolerance induction with recombinant allergens or allergen constructs". Curr Drug Targets Inflamm Allergy. 4 (5): 577–83. doi:10.2174/156801005774322207. PMID   16248826.
  4. ↑ Wiedermann U; Herz U; Baier K; Vrtala S; Neuhaus-Steinmetz U; Bohle B; Dekan G; Renz H; Ebner C; Valenta R; Kraft D. (November 1, 2007). "Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice". Int Arch Allergy Immunol. 126 (1): 68–77. doi:10.1159/000049496. PMID   11641608. S2CID   12838287.
  5. ↑ Repa A; Kozakova H; Hudcovic T; Stepankova R; Hrncir T; Tlaskalova-Hogenova H; Pollak A; Wiedermann U. (April 15, 2008). "Susceptibility to nasal and oral tolerance induction to the major birch pollen allergen Bet v 1 is not dependent on the presence of the microflora". Immunol. Lett. 117 (1): 50–56. doi:10.1016/j.imlet.2007.11.025. PMID   18241932.
  6. ↑ Wagner A; Förster-Waldl E; Garner-Spitzer E; Schabussova I; Kundi M; Pollak A; Scheiner O; Joachim A; Wiedermann U. (March 1, 2009). "Immunoregulation by Toxoplasma gondii infection prevents allergic immune responses in mice". Int J Parasitol. 39 (4): 465–72. doi:10.1016/j.ijpara.2008.09.003. PMID   18938169.
  7. ↑ Schabussova I; Hufnagl K; Wild C; Nutten S; Zuercher AW; Mercenier A; Wiedermann U. (February 24, 2011). "Distinctive anti-allergy properties of two probiotic bacterial strains in a mouse model of allergic poly-sensitization". Vaccine. 29 (10): 1981–90. doi:10.1016/j.vaccine.2010.12.101. PMID   21216308.
  8. ↑ Hoflehner E; Hufnagl K; Schabussova I; Jasinska J; Hoffmann-Sommergruber K; Bohle B; Maizels RM; Wiedermann U. (June 29, 2012). "Prevention of birch pollen-related food allergy by mucosal treatment with multi-allergen-chimers in mice". PLOS ONE. 7 (6): e39409. Bibcode:2012PLoSO...739409H. doi: 10.1371/journal.pone.0039409 . PMC   3387141 . PMID   22768077.
  9. ↑ Schabussova I1, Hufnagl K, Tang ML, Hoflehner E, Wagner A, Loupal G, Nutten S, Zuercher A, Mercenier A, Wiedermann U. (June 29, 2012). "Perinatal maternal administration of Lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy". PLOS ONE. 7 (7): e40271. Bibcode:2012PLoSO...740271S. doi: 10.1371/journal.pone.0040271 . PMC   3391241 . PMID   22792257.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  10. ↑ Wagner S; Jasinska J; Breiteneder H; Kundi M; Pehamberger H; Scheiner O; Zielinski CC; Wiedermann U. (November 1, 2007). "Delayed tumor onset and reduced tumor growth progression after immunization with a Her-2/neu multi-peptide vaccine and IL-12 in c-neu transgenic mice". Breast Cancer Res Treat. 106 (1): 29–38. doi:10.1007/s10549-006-9469-4. PMID   17203384. S2CID   23211112.
  11. ↑ Wiedermann U; Wiltschke C; Jasinska J; Kundi M; Zurbriggen R; Garner-Spitzer E; Bartsch R; Steger G; Pehamberger H; Scheiner O; Zielinski CC. (February 1, 2010). "A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study". Breast Cancer Res Treat. 119 (3): 673–83. doi:10.1007/s10549-009-0666-9. PMID   20092022. S2CID   9570606.
  12. ↑ "Imugene Appoints Distinguished Scientists to Scientific Advisory Board" (PDF). asx.com.au. 20 January 2014. Retrieved 3 December 2015.
  13. ↑ "Leading European Immunologist Prof Ursula Wiedermann Appointed Imugene Chief Scientific Officer". Imugene.com. 5 June 2015. Retrieved 3 December 2015.
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