Category Archives: Immunology

Immunology

Mestag Therapeutics Enlists Leading Cancer Biology and Immunology Advisors to Support Clinical Development of its … – GlobeNewswire

CAMBRIDGE, United Kingdom, Feb. 20, 2024 (GLOBE NEWSWIRE) -- Mestag Therapeutics (Mestag), a biotech company harnessing new insights into fibroblast-immune interactions to develop impactful treatments for patients, today announced the appointments of additional distinguished, world-leading advisors to guide the development of its lead program M300, a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor.

The new appointments expand Mestags advisors and comprise a unique group of investigators with extensive experience in the development of novel cancer therapies and specific expertise in the field of TLS biology in cancer. TLSs are aggregates of immune cells which provide a site of entry and education for immune cells in the tumor. The presence of TLS in tumors has recently become recognized as strongly predictive of improved patient outcomes and better response to therapy.1,2,3,4

Susan Hill, PhD, Chief Executive Officer of Mestag Therapeutics, said, Mestags M300 program opens up a new paradigm for the treatment of solid tumors. Advances in understanding TLS biology in cancer, and the associated benefit to patient outcomes, have enabled us to design a first-in-class program with the potential to benefit large numbers of patients with cancer. We are honored to work with such an eminent group of experts in this field to drive the program urgently into the clinic.

The newly appointed M300 advisors comprise Prof. Gabriele Bergers, group leader at the Flanders Institute for Biotechnology (VIB) Center for Cancer Biology and Professor of Oncology at the University of Leuven in Leuven, Belgium; Prof. Julie R. Brahmer, Director of the Thoracic Oncology Program, Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, as well as the Marilyn Meyerhoff Professor in Thoracic Oncology; Prof. Jeffrey L. Browning, Research Professor at the Boston University School of Medicine in the Departments of Virology, Immunology and Microbiology and Rheumatology; Prof. Wolf H. Fridman, Professor Emeritus of Immunology at Universit Paris-Cit, France; Prof. Catherine Sauts-Fridman, Professor Emeritus at Universit Paris-Cit; Prof. Elizabeth M. Jaffee, Professor of Oncology and Deputy Director at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; and Prof. Ignacio Melero, Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra.

Ignacio Melero, MD, PhD, advisor to Mestag and Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra, said, I look forward to collaborating with Mestag and to be a part of their world-class advisory team. I believe there is potential to develop transformative therapies for patients battling cancer. Mestags novel approach leverages known immunobiology, which for the first time, is being translationally harnessed to stimulate an anti-cancer immune environment within cancer tissue. Recent evidence supports the beneficial role of tertiary lymphoid structures in cancer, and the ability of a therapy to safely increase their presence could result in an efficacious intervention in patients with solid tumors.

Biographical information

Gabriele Bergers, PhD, is a Professor of Oncology at the University of Leuven and a group leader at the Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology in Leuven since 2016.Before her move to the VIB, shewas a Professor in the Department of Neurological Surgery and a PI in the Brain Tumor Research Center (BTRC) at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF), for 20 years. She has made seminal discoveries aboutperivasculartumor niches regarding the vasculature andtheimmune cell compartmentin regulating neovascularization, inflammation, and TLS formation in cancer and in revealing and understanding intrinsic and evasive resistance mechanisms of tumors to antiangiogenic immunotherapies. Dr. Bergers has received awards, including the Sidney Kimmel, the Sandler Opportunity, UCSF Breakthrough Biomedical Research, and the Judah Folkman. She hasacted as anexternal advisory board member fora number ofuniversities and pharmaceutical companies. Dr. Bergers wasthe Co-director of the Tumor Microenvironment Brain Tumor Center at UCSF and an advisor to the Max-Planck-Institute for Biomedicine in Muenster, Germany.She was a scientific co-founder of Oncurious.

Julie R. Brahmer, MD, is the Director of the Thoracic Oncology Program, Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, co-Leader of Cancer Immunology, as well as the Marilyn Meyerhoff Professor in Thoracic Oncology. She also directs the Kimmel Cancer Center on the Johns Hopkins Bayview campus and is co-principal investigator on Johns Hopkins' National Clinical Trials Network (NCTN) cooperative group grant. Dr. Brahmer is an active clinical leader in the treatment of lung cancer and mesothelioma. Dr. Brahmer's research and clinical practice focuses on the development of new therapies for the treatment of lung cancer and mesothelioma. She is a member of the American Society of Clinical Oncology, serves on the board of directors of the Society of Immunotherapy for Cancer, and is the Chair of the Eastern Cooperative Oncology Group (ECOG) Thoracic Committee. She is also on the medical advisory board of several lung cancer patient advocacy groups including LUNGevity, the Lung Cancer Research Fund, and Lung Cancer Research Foundation of America.

Jeffrey L. Browning, PhD, is a Research Professor at the Boston University School of Medicine in the Departments of Virology, Immunology and Microbiology and Rheumatology. He has a PhD in biochemistry from the University of Wisconsin. As a research scientist in the immunobiology discovery group at Biogen from 1984 to 2012, he centered on the tumor necrosis factor (TNF) family of regulatory molecules, including the discovery of the lymphotoxin, B-cell activating factor (BAFF) and TNF-like weak inducer of apoptosis (TWEAK) systems, and translation of modulators of the lymphotoxin pathway to the clinic in indications ranging from autoimmune disease and inflammatory bowel disease to oncology. He joined Boston University School of Medicine in 2013, with a current focus on altered vascular and stromal states in the perivascular compartment in the skin of systemic sclerosis and lupus patients and the impact on the pathology. Early in his career, he undertook postdoctoral work in the biophysics department of the University of Basel, Switzerland, using nuclear magnetic resonance to study membrane structure; and in the neurobiology department at the University of California, San Francisco researching the neuromuscular junction.

Wolf H. Fridman, MD, is Professor Emeritus of Immunology at Universit Paris-Cit. He is an expert in analysis of the tumor microenvironment, demonstrating that context, including functionality, location and density of the immune infiltrate in colorectal tumors, is the major prognostic factor for human cancers. He is involved in developing bioinformatic tools to quantify tumor microenvironment cells used to predict prognosis and immunotherapeutic responses in renal cell and colorectal cancers and sarcomas. His immune classification of soft tissue sarcoma tumors helped demonstrate that TLS and B cell signatures predict favorable clinical outcomes and therapeutic responses to anti-PD-1 therapy better than T cells, findings recently extended to other cancers treated with immune checkpoint blockers. These showed plasma cells generated inside TLS produce anti-tumor antibodies associated with a patients response to immunotherapy, opening the way for novel immune-based tools for efficient prognosis and therapy.

Catherine Sauts-Fridman, PhD, is Professor Emeritus at Universit Paris-Cit. She is the former Director of the Cancer, Immunology and Immunopathology department and Director of the Immunotherapy and Cancer team at Centre de Recherche des Cordeliers. Her research focuses on the heterogeneity of the immune and inflammatory components of the tumor microenvironment to identify new prognostic and theranostic markers. She carried out work in several fields: histocompatibility antigens, demonstration of the association of human leukocyte antigens (HLAs) with beta2-microglobulin and description of the 3rd histocompatibility locus in mice, H-2L and HLA-C in man, receptors for immunoglobulin G antibodies (biological activity and 3D structure), immuno-oncology (role of interleukin-17, TIME profiles of patients at risk of disease progression in localized kidney cancers, role of Tertiary Lymphoid Structures). She is the former President of the French Society of Immunology and European Federation of Immunological Societies. She founded the EFIS-EJI Ita Askonas Award to acknowledge female group leaders in immunology, and she founded the first European Congress of Immunology. She is Editor-in-Chief of La Revue Immunit et Cancer.

Elizabeth M. Jaffee, MD, is an internationally recognized expert in cancer immunology and pancreatic cancer. She is Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Co-Director of the Skip Viragh Pancreatic Cancer Center, and Associate Director of the Bloomberg Kimmel Institute for Cancer Immunotherapy. Her research focus is on developing novel immunotherapies for the treatment and prevention of pancreatic cancer. Prof. Jaffee is a past President of AACR and has served on several committees at the National Cancer Institute. She is Chief Medical Advisor to the Lustgarten Foundation for Pancreatic Cancer Research, and the Inaugural Director of the Convergence Institute for Integrating Technologies and Computational Sciences at Johns Hopkins. She is Chair of President Bidens Cancer Panel.

Ignacio Melero, MD, PhD, is Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra. He leads a group working in translational tumor immunotherapy with an emphasis on cell therapy, cytokine gene therapy, and immune-stimulatory monoclonal antibodies. Earlier in his career, Dr. Melero contributed to seminal discoveries in the function of Natural Killer cells, and T-cell co-stimulation via CD137 (4-1BB). Dr. Melero has been awarded the BIAL Prize of Medicine, the Conde de Cartagena Award from the Royal Academy of Medicine, Doctor Durantez LAIR Foundation Award and a CRI research award. He has served on advisory boards of Bristol Myers-Squibb, Roche-Genentech, AstraZeneca, Merck Serono and Boehringer Ingelheim, and holds research grants by Pfizer, Bristol Myers Squibb, and Alligator.

About Mestags M300 Program

M300 is a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor. TLSs are aggregates of immune cells that form in tumor tissue as part of our bodies natural anti-cancer mechanisms, and drive powerful immune responses by recruiting, educating, and activating new anti-tumor T and B-cells. Fibroblast populations play a key role in the induction and maintenance of TLSs. TLSs in tumors are strongly predictive of both improved patient outcomes across solid tumor types and better response to therapy.1,2,3,4

About Mestag Therapeutics

Mestag harnesses new insights into fibroblast-immune interactions to develop impactful treatments for patients. We are progressing a pipeline of sophisticated first-in-class antibodies designed to improve the lives of patients with cancer and inflammatory disease. Together with our collaboration partner Janssen Biotech, Inc., a Johnson & Johnson company, we are also identifying novel targets for future therapies.

Our founding investigators comprise global experts in inflammatory disease, cancer, computational biology and fibroblast biology from the University of Oxford, Brigham & Womens Hospital, Harvard Medical School and Cold Spring Harbor Laboratory. We are supported by leading life science investors SV Health Investors, Johnson & Johnson Innovation JJDC, Inc., Forbion, GV (formerly Google Ventures) and Northpond Ventures.

Mestag is headquartered in Cambridge, UK, and in 2021 was recognized on the Fierce 15 list of innovative biotechnology companies.

For further information please visit our website http://www.mestagtherapeutics.com

For enquiries, please contact:

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Mestag Therapeutics Enlists Leading Cancer Biology and Immunology Advisors to Support Clinical Development of its ... - GlobeNewswire

Immunology

Smoking has long-term effects on the immune system – Institut Pasteur

Like other factors such as age, sex and genetics, smoking has a major impact on immune responses. This is the finding recently made by a team of scientists at the Institut Pasteur using the Milieu Intrieur cohort of 1,000 healthy volunteers, established to understand variability in immune responses. In addition to its short-term impact on immunity, smoking also has long-term consequences. For many years after they have quit the habit, smokers are left with effects on some of their bodies' defense mechanisms acquired while smoking. These findings, which for the first time reveal a long-term memory of the effects of smoking on immunity, were published in the journal Nature on February 14, 2024.

Individuals' immune systems vary significantly in terms of how effectively they respond to microbial attacks. But how can this variability be explained? What factors cause these differences? "To answer this key question, we set up the Milieu Intrieur cohort comprising 1,000 healthy individuals aged 20 to 70 in 2011," comments Darragh Duffy, Head of the Translational Immunology Unit at the Institut Pasteur and last author of the study. While certain factors such as age, sex and genetics are known to have a significant impact on the immune system, the aim of this new study was to identify which other factors had the most influence."

The scientists exposed blood samples taken from individuals in the Milieu Intrieur cohort to a wide variety of microbes (viruses, bacteria, etc.) and observed their immune response by measuring levels of secreted cytokines(1). Using the large quantities of data gathered for individuals in the cohort, the team then determined which of the 136 investigated variables (body mass index, smoking, number of hours' sleep, exercise, childhood illnesses, vaccinations, living environment, etc.) had the most influence on the immune responses studied. Three variables stood out: smoking, latent cytomegalovirus infection(2) and body mass index. "The influence of these three factors on certain immune responses could be equal to that of age, sex or genetics," points out Darragh Duffy.

As regards smoking, an analysis of the data showed that the inflammatory response, which is immediately triggered by infection with a pathogen, was heightened in smokers, and moreover, the activity of certain cells involved in immune memory was impaired. In other words, this study shows that smoking disrupts not only innate immune mechanisms, but also some adaptive immune mechanisms.

A comparison of immune responses in smokers and ex-smokers revealed that the inflammatory response returned to normal levels quickly after smoking cessation, while the impact on adaptive immunity persisted for 10 to 15 years. This is the first time it has been possible to demonstrate the long-term influence of smoking on immune responses.

Darragh DuffyHead of the Translational Immunology Unit at the Institut Pasteur and last author of the study

Basically, the immune system appears to have something resembling a long-term memory of the effects of smoking. But how? "When we realized that the profiles of smokers and ex-smokers were similar, we immediately suspected that epigenetic processes were at play(3)," says Violaine Saint-Andr, a bioinformatician in the Institut Pasteur's Translational Immunology Unit and first author of the study. "We demonstrated that the long-term effects of smoking on immune responses were linked to differences in DNA methylation(4) with the potential to modify the expression of genes involved in immune cell metabolism between smokers, ex-smokers and non-smokers." It therefore appears that smoking can induce persistent changes to the immune system through epigenetic mechanisms.

This is a major discovery elucidating the impact of smoking on healthy individuals' immunity and also, by comparison, on the immunity of individuals suffering from various diseases.

Violaine Saint-AndrBioinformatician in the Institut Pasteur's Translational Immunology Unit and first author of the study

(1) proteins secreted by a large number of immune cells to communicate among themselves and participate in immune defense.

(2) a virus in the herpes family that is often asymptomatic though dangerous to fetuses.

(3) changes in DNA that affect how genes are expressed, i.e. how they are used by cells.

(4) methylation is a type of chemical modification. Methyl groups position themselves on DNA, changing the way in which the genome is read in the cell.

Smoking changes adaptive immunity with persistent effects, Nature, February 14, 2024

Violaine Saint-Andr1,2*, Bruno Charbit3, Anne Biton2, Vincent Rouilly4, Cline Possm1, Anthony Bertrand1,5, Maxime Rotival6, Jacob Bergstedt6,7,8, Etienne Patin6, Matthew L. Albert9, Lluis Quintana-Murci6,10, Darragh Duffy1,3*, and the Milieu Interieur Consortium

1Translational Immunology Unit, Department of Immunology, Institut Pasteur, Universit Paris Cit, Paris 75015, France. 2Bioinformatics and Biostatistics HUB, Department of Computational Biology, InstitutPasteur, Universit Paris Cit, Paris 75015, France. 3Cytometry and Biomarkers UTechS, Center for Translational Research, Institut Pasteur, Universit Paris Cit, Paris 75015, France. 4DATACTIX, Paris, France. 5Frontiers of Innovation in Research and Education PhD Program, LPI Doctoral School, Universit Paris Cit, Paris, France. 6Institut Pasteur, Universit Paris Cit, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris 75015, France. 7Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 9HIBIO, San Francisco, California, USA. 10Chair Human Genomics and Evolution, Collge de France, Paris 75005, France. *Corresponding author

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Smoking has long-term effects on the immune system - Institut Pasteur

Immunology

Spring Allergies Attack More Than Just Your Nose – ACAAI Public Website – American College of Allergy Asthma and Immunology

February 15, 2024

Your nose, eyes, respiratory system and skin can all be involved when spring allergies hit

ARLINGTON HEIGHTS, Ill. (February 15, 2024) If you suffer from spring allergies, you already know that you tend to feel miserable once pollen season descends. But did you know that allergies can affect many different systems within your body and that theyre all interconnected?

Spring allergens such as pollen, mold spores and other airborne particles not only trigger nasal allergies, but also can have a profound effect on a variety of allergic conditions including asthma and eczema, says allergist Gailen Marshall, MD, PhD, president of the American College of Allergy, Asthma and Immunology (ACAAI). Understanding how all the allergic responses are interconnected is crucial for effectively managing and improving the overall quality of life for people who are affected.

How will you feel the effects?

Nasal allergies: The image that pops to mind when you hear spring allergies is someone sneezing and blowing their nose. Inhaled pollen can trigger an allergic reaction in susceptible people, leading to symptoms like sneezing, itching and nasal congestion. Nasal allergies are commonly referred to as hay fever although there is no connection to either hay or fever. The impact of these allergies isnt limited to the respiratory tract.

Asthma flares: For people with asthma, exposure to spring allergens can make their symptoms much worse. Pollen and other airborne allergens can irritate the airways, leading to a rapid tightening of the airways and increased inflammation over time. This aggravation can result in wheezing, coughing, and/or difficulty breathing. The link between nasal allergies and asthma, sometimes known as the allergic march, shows the progression in some individuals.

Eczema: Beyond the respiratory system, spring allergens and warmer temperatures can also impact the skin. Eczema, a chronic inflammatory skin condition, may worsen during the spring months. Pollen and other environmental allergens can trigger flare-ups in individuals with sensitive skin. The connection between environmental allergies and skin conditions emphasizes the need for a comprehensive approach to managing allergic diseases.

Eye allergies: Seasonal allergic conjunctivitis (SAC) is by far the most common type of eye allergy. Patients can experience symptoms in spring, summer and/or fall, depending on the type of plantpollensin the air. Typical symptoms include itching, redness, burning and clear, watery discharge. People with SAC may have chronic dark circles (known as allergic shiners) under their eyes. The eyelids may be puffy, and bright lights may be bothersome. SAC symptoms often accompany the runny nose, sneezing and nasal congestion associated with hay fever and other seasonal allergies.

Whats an allergic person to do?

Get the right medications: Although people react differently to different allergens, often the symptoms look very similar. If you find yourself reacting in the same way at the same time every year, you might have allergies and the right medication can help. Medications such as antihistamines, nasal corticosteroids, and bronchodilators play a crucial role in alleviating symptoms associated with spring allergies. These therapies can help manage both respiratory and skin flares, along with stuffiness, sneezing and itchy eyes.

Avoid your allergens: Once you know what you have an allergic reaction to, you can work to avoid that substance. Measures such as keeping windows shut to keep out pollen, taking a shower at night, and washing your clothes after being outside around pollen, can all help ease symptoms. If you have eczema, moisturizing often is key to reducing itching, and avoid fabrics that irritate your skin. For eye allergies, artificial tears can temporarily wash allergens from the eyes and moisten them.

See an allergist: A board-certified allergist can work with you to identify your personal allergen sensitivity profile and get your symptoms under control. Allergists can do testing to determine what is causing your symptoms, and develop a plan tailored to your needs. Your allergist may suggest allergen immunotherapy, either in shot or tablet form. Immunotherapy can be a long-term solution that can modify your immune systems response to specific allergens.

Although symptoms may not always be severe, allergies andasthmaare diseases and should be treated that way. Many people with allergies, asthma or eczema simply dont realize how much better they can feel. To locate an allergist in your area, visit AllergyAndAsthmaRelief.org.

About ACAAI ACAAI is a professional medical organization of more than 6,000 allergists-immunologists and allied health professionals, headquartered in Arlington Heights, Ill. The College fosters a culture of collaboration and congeniality in which its members work together and with others toward the common goals of patient care, education, advocacy, and research. ACAAI allergists are board-certified physicians trained to diagnose allergies and asthma, administer immunotherapy, and provide patients with the best treatment outcomes. For more information and to find relief, visit AllergyandAsthmaRelief.org. Join us on Facebook, Pinterest, Instagram, and Twitter/X.

Allergy, Allergy Symptoms, Allergy Treatment

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Spring Allergies Attack More Than Just Your Nose - ACAAI Public Website - American College of Allergy Asthma and Immunology

Immunology

Theratechnologies Announces Publication in Frontiers in Immunology that Deepens Understanding of Sudocetaxel … – GlobeNewswire

MONTREAL, Feb. 20, 2024 (GLOBE NEWSWIRE) -- Theratechnologies Inc. (Theratechnologies or the Company) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, today announced the publication of a peer-reviewed article in Frontiers in Immunology that enhances understanding of the molecular mechanism of action of sudocetaxel zendusortide (also known as TH1902) as a potential anticancer treatment. Sudocetaxel zendusortide is an investigational, first-in-class peptide-drug conjugate (PDC) that targets the sortilin receptor (SORT1) and expedites the internalization and delivery of the cytotoxic payload (docetaxel) directly into cancer cells.

The article, Sudocetaxel Zendusortide (TH1902) triggers the cGAS/STING pathway and potentiates anti-PD-L1 immune-mediated tumor cell killing appears in the Cancer Immunity and Immunotherapy section of the February (Volume 15) issue of the journal. It reports on preclinical research in which sudocetaxel zendusortide induced complete and prolonged tumor regression in a triple-negative breast cancer (TNBC)-derived xenograft tumor model and demonstrated tumor regression associated with growth inhibition and immune cell infiltration in a cold murine (syngeneic) tumor model. Additionally, combining sudocetaxel zendusortide with an anti-PD-L1 checkpoint inhibitor led to increases in tumor growth inhibition and median animal survival.

The results published in Frontiers in Immunology demonstrate that sudocetaxel zendusortide exerts its antitumor activity, in part, through modulation of the immune tumor microenvironment, said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies, and one of the papers co-authors. Our findings reinforce that combining this novel peptide-drug conjugate with anti-PD-L1 checkpoint inhibitor therapy may yield improved clinical outcomes, with potentially profound implications for patients across various cancer types.

An important aspect of our research is the activation of an antitumor immunity process through involvement of the cGAS/STING pathway, a key regulator in the cancer-immunity cycle, commented Prof. Borhane Annabi, Chair in Cancer Prevention and Treatment in the Chemistry Department at the Universit du Qubec Montral, and a co-author of the Frontiers in Immunology paper. Although the animal tumor model we worked with is considered a non-immunogenetic, or cold tumor model, we observed a net increase in leukocyte infiltration within sudocetaxel zendusortide-treated tumors, especially for tumor-infiltrating lymphocytes and tumor-associated macrophages. This realization supports the rationale for further exploration of the combination of sudocetaxel zendusortide with immunotherapy.

The article can be accessed online here.

About Immunotherapy in Cold and Hot Tumors

Immunotherapies have significantly improved the treatment of cancer. Researchers continue to explore the power of the immune system to find and destroy cancer cells. Hot tumors show signs of inflammation, meaning the tumor has already been infiltrated by immune cells rushing to fight the cancerous cells. Only a few types of cancers are considered to be hot. Cold tumors have not yet been infiltrated with T cells. This signals that the immune response is not working, making it difficult to provoke an immune response with immunotherapies. Most cancers of breast, ovary, prostate, pancreas, and brain (e.g., glioblastoma [GBM]) are cold tumors, and are largely treated with traditional therapies like radiation and chemotherapy. As a result, researchers have sought to understand how to turn cold tumors hot by reversing the suppressive microenvironment surrounding cold tumors and by attracting more of the right anti-tumor lymphocytes.

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Companys broader licensed oncology platform. As a new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial in individuals with advanced ovarian cancer.

Theratechnologies has established the SORT1+ TechnologyTMplatform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a scavenger receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

About Theratechnologies

Theratechnologies (TSX: TH) (NASDAQ: THTX) is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs. Further information about Theratechnologies is available on the Company's website at http://www.theratech.com, on SEDAR+ at http://www.sedarplus.caand on EDGAR at http://www.sec.gov. Follow Theratechnologies on Linkedinand X (formerly Twitter).

Forward-Looking Information

This press release contains forward-looking statements and forward-looking information (collectively, the Forward-Looking Statements) within the meaning of applicable securities laws, that are based on managements beliefs and assumptions and on information currently available to it. You can identify forward-looking statements by terms such as may, will, should, could, promising, would, outlook, believe, plan, envisage, anticipate, expect and estimate, or the negatives of these terms, or variations of them. The Forward-Looking Statements contained in this press release include, but are not limited to, statements regarding the combination of sudocetaxel zendusortide with anti-PD-L1 checkpoint inhibitor therapy which may yield improved clinical outcomes, the potential treatment of various types of cancer with sudocetaxel zendusortide, the development of PDCs resulting from the SORT1+ TechnologyTMplatform and our estimates regarding the expression of SORT1 in various types of cancer. Although the Forward-Looking Statements contained in this press release are based upon what the Company believes are reasonable assumptions in light of the information currently available, investors are cautioned against placing undue reliance on these statements since actual results may vary from the Forward-Looking Statements contained in this press release. These assumptions include, without limitation, that the results observed in pre-clinical testing will be replicated into humans, sudocetaxel zendusortide will be able to treat various types of cancer, the Company will be successful in developping addtional PDCs from the SORT1+ TechnologyTMplatform and positive safety and efficacy results will be observed from the current Phase 1 clinical trial studying sudocetaxel zendusortide. Forward-Looking Statements assumptions are subject to a number of risks and uncertainties, many of which are beyond the Companys control, that could cause actual results to differ materially from those that are disclosed in or implied by such Forward-Looking Statements. These risks and uncertainties include, but are not limited to, the inability of sudocetaxel zendusortide to demonstrate efficacy results when used in human subjects, limitations in the types of cancer for which sudocetaxel zendusortide could be used and limitations in the capacity of the Company to develop new PDCs. We refer current and potential investors to the Risk Factors section of our Annual Information Form dated February 27, 2023, available on SEDAR+ atwww.sedarplus.caand on EDGAR atwww.sec.govas an exhibit to our report on Form 40-F dated February 28, 2023, under Theratechnologies public filings. The reader is cautioned to consider these and other risks and uncertainties carefully and not to put undue reliance on forward-looking statements. Forward-Looking Statements reflect current expectations regarding future events and speak only as of the date of this press release and represent our expectations as of that date.

We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise, except as may be required by applicable law.

Contacts:

Media inquiries: Julie Schneiderman Senior Director, Communications & Corporate Affairs communications@theratech.com 1-514-336-7800

Investor inquiries: Philippe Dubuc Senior Vice President and Chief Financial Officer pdubuc@theratech.com 1-438-315-6608

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Immunology

Shikhar Mehrotra named co-leader of Cancer Biology and Immunology research program at MUSC Hollings – The Cancer Letter

Shikhar Mehrotra, professor of surgery and Cecilia and Vincent Peng Endowed Chair in melanoma and cutaneous oncology, will take on the role of co-leader of the Cancer Biology and Immunology Research Program at MUSC Hollings Cancer Center, alongside Philip Howe, professor and chair of the Department of Biochemistry & Molecular Biology, and Sophie Paczesny, professor in the Department of Microbiology & Immunology.

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Immunology

Gut Microbiome Benefits of Breast Milk Revealed in Mouse Study – Technology Networks

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An immune component of breast milk known as the complement system shapes the gut environment of infant mice in ways that make them less susceptible to certain disease-causing bacteria, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

The researchers found that mouse pups that nursed from lactating mice whose breast milk lacked a key complement protein had different gut microbe populations than pups that nursed on standard mouse breast milk, making them highly vulnerable toCitrobacter rodentium,a bacterium that infects the guts of mice.Citrobacter rodentiumis similar to certain types of diarrhea-causingE. colithat can infect humans but not mice.

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The researchers experiments suggest that mouse breast milks complement components boost mouse infant health by directly eliminating some types of gut-dwelling bacteria. This reshaping of the gut microbiota leaves the infant mice far less susceptible toCitrobacter rodentiuminfection, thus protecting the young from certain infectious threats. The reshaping activity is not dependent on antibodies, in contrast to the way complement components are thought to typically work.

The researchers also confirmed in separate in vitro analyses that human breast milk contains these complement components, which demonstrated similar activity in targeting specific bacteria.

Taken together, these findings shed light on the mechanisms of how breast milk functions to provide protection from certain bacterial infections.

Thestudywas published online January 18 in the journalCell.

These findings reveal a critical role for breast milk complement proteins in shaping offsprings gut microbecompositions and protecting against bacterial infection in the gutin early life, says study senior author Fengyi Wan, PhD, a professor in theBloomberg SchoolsDepartment of Biochemistry and Molecular Biology. This represents an important expansion of our understanding of breast milks protective mechanisms.

The studys first author is Dongqing Xu, PhD, an assistant scientist in Wans research group.

Breastfeeding has many known and suspected benefits. It provides excellent nutrition to infants and appears to protect against some short-term or long-term illnesses. Breast milk is also known to help protect against common infections by sharing antibodies and white blood cells from the mother.

Breast milk also contains complement proteins that can work with, or complement, antibodies in attacking bacteria. While complement proteins that circulate in the blood have been the focus of much research, complement proteins in breast milk have been far less studied, and until now their role has been unclear.

In the new study, Wan and his team used engineered mice that lacked critical complement genes. They found that milk from female mice of this type left several-weeks-old mouse pupseven those with normal complement geneshighly susceptible to colitis, often lethal, fromCitrobacter rodentiuminfections.By contrast, pups feeding on normal, complement-containing milk showed only minor and transient signs of gut infection.

The team discovered that this protective effect of breast milk complement proteins depends on their capacity in shaping infant gut microbiota. The complement proteins kill certain gut bacterial species, and this culling of microbes creates an overall gut environment in which harmful inflammation is much less likely in the presence ofCitrobacter rodentium.

Gut microbiota is of great importance to health, says Wan. Breast milk complement proteins contribute crucially to the establishment of a protective gut microbiota during the early stages of development, promoting infant health and defending against pathogens.

The study also appears to mark an advance in basic immunology. Complement proteins in blood, although known to be capable of causing direct damage to bacterial cells, have been thought to typically work in partnership with antibodies in a specific immune response. However, Wan and his team showed that this breast milk complement activity against bacteria does not require antibodies and is a nonspecific immune response.

This opens the door to a lot of new investigations, for example, elucidating the specific complement biology in breast milk and comparing that to complement biology in the blood, andassessingthe role of complement beyond the antibody-dependent specific immune system, Wan says.

Reference:Xu D, Zhou S, Liu Y, Scott AL, Yang J, Wan F. Complement in breast milk modifies offspring gut microbiota to promote infant health. Cell. 2024:S0092867423013843. doi:10.1016/j.cell.2023.12.019

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Gut Microbiome Benefits of Breast Milk Revealed in Mouse Study - Technology Networks

Immunology

Research on Immunological Diseases Launches with Hungarian Participation – Hungary Today

A project studying the impact of infectious diseases on the development of immunological diseases is being launched with the participation of the HUN-REN SZBK Systems Biology Research Group, announced the Szeged Biological Research Center (SZBK), a member of the Hungarian Research Network (HUN-REN).

Within the ID-DarkMatter-NCD project, funded by the European Unions Framework Program for Research and Innovation, researchers are investigating why certain infectious diseases are followed by immunological diseases. The consortium is led by Thomas Vogl from the Medical University of Vienna and the team is made up of top experts in immunology, genetics, and data science. The Systemic Immunology Research Group at the SZBK is coordinating the genetic analysis of patients within the project.

To achieve this, the team will analyze the antibody-mediated immune response to around 600,000 antigens from 6,000 patients. Diseases selected for detailed analysis include post-COVID syndrome, inflammatory autoimmune disease affecting the central nervous system, multiple sclerosis, chronic fatigue syndrome, autoimmune disease with inflammatory lesions of the joints, rheumatoid arthritis, chronic autoimmune disease affecting various organs of the body, systemic lupus erythematosus, and inflammatory bowel disease.

The 60-month project, funded by the Horizon Europe program with EUR 8.4 million, involves 12 European consortium partners, including the University of Basel as a Swiss co-partner with additional funding of around EUR 1.2 million.

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Via MTI, Featured image: Pixabay

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Research on Immunological Diseases Launches with Hungarian Participation - Hungary Today