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Julianna Lisziewicz (born 1959) is a Hungarian immunologist. Lisziewicz headed many research teams that have discovered and produced immunotheraputic drugs to treat diseases like
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
and chronic infections like
HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
. Some of these drugs have been successfully used in
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s.


Education

Lisziewicz graduated from
Budapest University of Technology The Budapest University of Technology and Economics ( or in short ), official abbreviation BME, is a public research university located in Budapest, Hungary. It is the most significant university of technology in the country and is considered t ...
in
Budapest, Hungary Budapest is the Capital city, capital and List of cities and towns of Hungary, most populous city of Hungary. It is the List of cities in the European Union by population within city limits, tenth-largest city in the European Union by popul ...
with an MSc in
Chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...
and
Biology Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...
in 1982. She went on to earn her Ph.D. in
Molecular Biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
at the
Max-Planck Institute The Max Planck Society for the Advancement of Science (; abbreviated MPG) is a formally independent non-governmental and non-profit association of German research institutes. Founded in 1911 as the Kaiser Wilhelm Society, it was renamed to the M ...
in
Germany Germany, officially the Federal Republic of Germany, is a country in Central Europe. It lies between the Baltic Sea and the North Sea to the north and the Alps to the south. Its sixteen States of Germany, constituent states have a total popu ...
. Lisziewicz did post-doctoral research at the Max-Planck Institute of Experimental Medicine from 1985 to 1989.


Career


National Institutes of Health

Lisziewicz worked at the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
(NIH) from 1989 to 1995. During her time working at the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
she was the Head of the Antiviral Unit at the Laboratory of Tumor Cell Biology.


Research Institute for Genetic and Human Therapy (RIGHT)

In 1995, Lisziewicz and her colleague Franco Lori founded the Research Institute for Genetic and Human Therapy (RIGHT), where Lisziewicz worked as the Director. RIGHT is a non-profit organization based in the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
and
Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...
that funds research to develop immunologic technologies, create new therapies, and research
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
s for many chronic diseases like
HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
. RIGHT strives to quickly put their discoveries to use in patient treatments.


Genetic Immunity, Inc.

Lisziewicz founded Genetic Immunity, Inc., and worked as the President and the CEO of the company. Genetic Immunity is a private clinical-stage biotechnology company in the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
and
Hungary Hungary is a landlocked country in Central Europe. Spanning much of the Pannonian Basin, Carpathian Basin, it is bordered by Slovakia to the north, Ukraine to the northeast, Romania to the east and southeast, Serbia to the south, Croatia and ...
. Genetic Immunity works to create and commercialize immunotherapeutic biologics to treat chronic viral infections,
allergies 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 Allergic rhinitis, hay fever, Food allergy, food al ...
, and
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
s to prolong the life of the patient and improve their quality of life.


TREOS Bio

TREOS Bio is a company that develops precision
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
s to treat and prevent cancer using computational immune-oncology. Lisziewicz worked as the Chief Scientific Officer of TREOS Bio.


Research


Antisense oligonucleotides

While working at the
National Institute of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Servic ...
, Lisziewicz worked to find a
gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...
approach to treat
HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
. She based her research on discovering if small portions of gene-stopping
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
(called antisense
oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase ...
s) could be created to bind up the viral
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
in
retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
es like HIV so that the virus could not make more copies of itself to continue the infection. Small pieces of
messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
(or mRNA) carry a copy of the cell's DNA to the
ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...
s where the mRNA directs the ribosomes to create the
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s that the cells need.
Virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
es (like HIV) have their own set of mRNA, and they use the ribosomes of the cell they infected to make new viruses to propagate the infection throughout the body. Lisziewicz's idea was to create antisense oligonucleotides that are complementary to the HIV's viral mRNA. These
complementary DNA In genetics, complementary DNA (cDNA) is DNA that was reverse transcribed (via reverse transcriptase) from an RNA (e.g., messenger RNA or microRNA). cDNA exists in both single-stranded and double-stranded forms and in both natural and engin ...
pieces can bind to the HIV viral mRNA and prevent the HIV virus from replicating itself. The use of antisense oligonucleotides worked very well in
cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...
s, and was quickly transferred to
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s.


DermaVir

DermaVir immunotherapy was created during Lisziewicz's research at the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
in
Bethesda, Maryland Bethesda () is an unincorporated, census-designated place in southern Montgomery County, Maryland, United States. Located just northwest of Washington, D.C., it is a major business and government center of the Washington metropolitan region ...
. She worked to produce gene and antisense therapies to treat
HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
, and researched how the
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
controls HIV in tissue culture and in monkey models. She applied these results to the treatment of HIV patients in clinical trials. Lisziewicz discovered and headed the preclinical and clinical development of DermaVir HIV immunotherapy. Under Lisziewicz's direction, DermaVir successfully completed a Phase 2 clinical trial. DermaVir is a
topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
vaccine that is applied with a patch to the skin. It is a new
immunization Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the antigen, immunogen). When this system is exposed to molecules that are foreign to the body, called ' ...
strategy that uses
dendritic cell A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...
s to increase viral
antigen 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. ...
production. DermaVir contains a
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
that expresses all of the HIV
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
except
integrase Retroviral integrase (IN) is an enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme ...
. This stimulates an
immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...
to attack the cells infected with HIV. DermaVir has been proven safe and immunogenic in several clinical trials, one of which was in collaboration with the Division of AIDS (DAIDS). In one trial, Lisziewicz's research team compared the
immunogenicity Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injecti ...
of topical-based and
ex vivo refers to biological studies involving tissues, organs, or cells maintained outside their native organism under controlled laboratory conditions. By carefully managing factors such as temperature, oxygenation, nutrient delivery, and perfusi ...
dendritic cell-based DermaVir in
rhesus macaque The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies split between two groups, the Chinese-derived and the Indian-derived. Generally brown or g ...
s. As a result, it was discovered that both vaccinations induced CD4 helper T cells and CD8 memory T cells that are specific to
simian immunodeficiency virus Simian immunodeficiency virus (SIV) is a species of retrovirus that cause persistent infections in at least 45 species of non-human primates. Based on analysis of strains found in four species of monkeys from Bioko Island, which was isolated fr ...
. The CD4 helper T cells and CD8 memory T cells were identified using an
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
skin test and an
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
intracellular cytokine-based assay. The topical DermaVir vaccine is an improvement upon the
ex vivo refers to biological studies involving tissues, organs, or cells maintained outside their native organism under controlled laboratory conditions. By carefully managing factors such as temperature, oxygenation, nutrient delivery, and perfusi ...
dendritic cell- based immunization that could offer a new alternative therapy for patients with HIV.


PolyPEPI™

An investigation Lisziewicz was involved with when she was working at TREOS Bio is how
human leukocyte antigen The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histo ...
(HLA) genes regulate immune responses. This research led to the development of a computational immune-oncology technology that can determine a patient's natural
T cell T cells (also known as T lymphocytes) are an important part 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 receptor (TCR) on their cell ...
response to tumor
antigen 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. ...
s. As a result, TREOS Bio found there was a correlation between a patient's HLA gene sequence and how well their
immunotherapies 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 immunotherap ...
worked. PolyPEPI™ immunotherapies to treat a number of cancer indications were created by TREOS Bio using the computational immune-oncology.


Langerhans cell-targeting DNA vaccines

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in t ...
s are a natural agent of
antigen 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. ...
release. They are the precursors of
dendritic cell A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...
s in the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
and
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
. Lisziewicz and her team developed synthetic nanoparticles that act like
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
s and specially target
Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in t ...
s in
epidermal The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
cell cultures. When these nanoparticles are applied topically to human subjects, a strong
immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...
was observed. This
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
has been clinically proven, and it opens the door for more new dendritic cell-targeting vaccines to be created for the treatment of cancers.


References

{{DEFAULTSORT:Lisziewicz, Julianna 1959 births Living people Molecular biologists Hungarian women physicians Budapest University of Technology and Economics alumni Women immunologists Hungarian immunologists Physicians from Budapest