Review
Pharmacology & Pharmacy
Yifeng Cao, Chuyang Chen, Yi Tao, Weifeng Lin, Ping Wang
Summary: Triple-negative breast cancer (TNBC) is characterized by extensive tumor heterogeneity at both the pathologic and molecular levels, leading to increased mortality of patients due to accelerated aggressiveness and terrible metastasis. Hindered by the negative expression of certain receptors, targeted therapy has been challenging, but the higher immune response in TNBC compared to other breast cancer types makes it suitable for immunotherapy.
Review
Medicine, General & Internal
Hyeryeon Choi, Kwangsoon Kim
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Current treatment options are limited and variable response to chemotherapy exists due to disease heterogeneity. This review discusses FDA-approved targeted therapies for TNBC, as well as novel theranostic approaches using nanocarriers. These approaches aim to improve diagnosis and treatment of TNBC by enabling targeted drug delivery and visualization of the lesion.
Review
Nanoscience & Nanotechnology
Siyan Liu, Jing Li, Lin Gu, Kunzhe Wu, Hua Xing
Summary: Chemoimmunotherapy shows promise for treating TNBC, but challenges remain in improving efficacy and reducing side effects.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Oncology
Hanwen Wang, Huilin Ma, Richard J. Sove, Leisha A. Emens, Aleksander S. Popel
Summary: This study introduces a modular quantitative systems pharmacology (QSP) platform for predicting immunotherapy efficacy and identifying predictive biomarkers. Virtual clinical trials were conducted using a virtual patient cohort generated by the model, with retrospective analysis and model validation based on clinical trial data.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Chemistry, Medicinal
Elizabeth R. Berger, Tristen Park, Angeleke Saridakis, Mehra Golshan, Rachel A. Greenup, Nita Ahuja
Summary: Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes in breast cancer with dismal prognosis, lacking targeted therapy options. Immunotherapy, particularly immune checkpoint inhibitor therapy, has revolutionized the treatment landscape for TNBC, showing promising results.
Review
Biochemistry & Molecular Biology
Yang Liu, Yueting Hu, Jinqi Xue, Jingying Li, Jiang Yi, Jiawen Bu, Zhenyong Zhang, Peng Qiu, Xi Gu
Summary: Immunotherapy has emerged as a promising strategy for treating triple-negative breast cancer (TNBC), which stimulates the immune system to kill tumor cells and offers new hope for patients. Breakthroughs in immune checkpoint inhibitors (ICIs) have led to individualized immunotherapy schedules and the combination with other treatment methods to overcome drug resistance.
Article
Oncology
Renato Brito Baleeiro, Peng Liu, Louisa S. Chard Dunmall, Carmela Di Gioia, Ai Nagano, Lauren Cutmore, Jun Wang, Claude Chelala, Lydon Wainaina Nyambura, Peter Walden, Nicholas Lemoine, Yaohe Wang
Summary: This study successfully identified immunogenic neoantigens and generated neoantigen-specific CD8+T cells capable of recognizing human triple-negative breast cancer cells. Using an oncolytic virus as a delivery system, the researchers demonstrated that vaccination with neoantigens can induce a specific CD8+T cell response, slow tumor growth, and increase survival in a mouse model of TNBC. This study provides a promising approach for the development of neoantigen-based immunotherapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Dorota Kwapisz
Summary: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options, but it shows higher immunogenicity, tumor-infiltrating lymphocytes (TILs) enrichment, and programmed cell death ligand 1 (PD-L1) expression which make it more suitable for immune checkpoint blockade therapy. Patients with PD-L1-positive TNBC subgroup may benefit the most from immune checkpoint inhibitor (ICI) treatment, and ICI given as first-line treatment in advanced TNBC shows better results than in later lines of treatment. Exciting results have been seen with pembrolizumab in early-stage TNBC, indicating potential approval in (neo)adjuvant settings in the near future.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Review
Oncology
Hongnan Mo, Binghe Xu
Summary: Triple-negative breast cancer is the most aggressive subtype of breast cancer, where chemotherapy shows activity in some patients but drug resistance remains a challenge. Significant progress in genetic analysis has led to the identification of novel targets and improved precision in therapeutic interventions, advancing treatment strategies.
FRONTIERS OF MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Onyinyechi Obidiro, Gantumur Battogtokh, Emmanuel O. Akala
Summary: Triple negative breast cancer (TNBC) is a subtype of breast cancer that lacks estrogen receptors, progesterone receptors, and human epidermal growth factor receptors. The survival rate for TNBC is generally lower than other subtypes. Chemotherapy is the most common treatment option, but resistance to drugs and off-target toxicity pose challenges. Researchers, clinicians, and pharmaceutical companies must collaborate to develop effective treatments for TNBC. Nanotechnology has shown promise as a potential solution for improving TNBC treatment.
Review
Oncology
Jakub Wesolowski, Anna Tankiewicz-Kwedlo, Dariusz Pawlak
Summary: This review summarizes the safety and clinical effectiveness of new biological drugs in stimulating the immune system to fight cancer, particularly in triple-negative breast cancer (TNBC). The introduction of monoclonal antibodies in standard cancer therapies has shown to increase treatment response rates and extend the lives of cancer patients. Recent clinical trials have highlighted the potential of immunotherapy using monoclonal antibodies in difficult-to-treat TNBC, with some trials resulting in the approval of immunotherapeutic agents for TNBC therapy.
Review
Immunology
Yiwen Zheng, Shujin Li, Hongchao Tang, Xuli Meng, Qinghui Zheng
Summary: The emergence of immunotherapy has revolutionized the treatment of triple-negative breast cancer (TNBC). However, the heterogeneity of TNBC leads to varying efficacy of immunotherapy, with only certain patients benefiting from it. This article focuses on the mechanisms of immune response and summarizes the immune evasion mechanisms in TNBC, including loss of tumor-specific antigen, antigen presentation deficiency, and failure to initiate an immune response. Moreover, the aberrant activation of immune-critical signaling pathways contributes to an immunosuppressive tumor microenvironment. The review aims to elucidate the molecular mechanisms of drug resistance in TNBC, identify potential targets to reverse drug resistance, and lay a foundation for biomarker research to predict immune efficacy and select breast cancer populations for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Shuangli Zhu, Yuze Wu, Bin Song, Ming Yi, Yuheng Yan, Qi Mei, Kongming Wu
Summary: Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, lacks expression of estrogen receptor, progesterone receptor, and HER2. Although chemotherapy is the main treatment for TNBC, its effectiveness is limited. Various targeted therapies, including inhibitors of the PI3K/AKT/mTOR pathway, epidermal growth factor receptor inhibitors, Notch inhibitors, poly ADP-ribose polymerase inhibitors, and antibody-drug conjugates, have emerged. Additionally, immune checkpoint inhibitors such as pembrolizumab, atezolizumab, and durvalumab, are being extensively investigated. This review summarizes recent advances in targeted therapy and immunotherapy in TNBC, aiming to serve as a reference for future development of personalized treatment for TNBC patients.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Review
Oncology
Yun Li, Huajun Zhang, Yulia Merkher, Lin Chen, Na Liu, Sergey Leonov, Yongheng Chen
Summary: Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer with a poor prognosis. Current treatment options are limited, but targeted therapies focusing on DNA repair pathways, androgen receptor signaling pathways, kinases, and immunotherapy have shown promise.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Health Care Sciences & Services
Christos Damaskos, Nikolaos Garmpis, Anna Garmpi, Konstantinos Nikolettos, Panagiotis Sarantis, Vasiliki E. Georgakopoulou, Afroditi Nonni, Dimitrios Schizas, Efstathios A. Antoniou, Michalis Karamouzis, Nikos Nikolettos, Konstantinos Kontzoglou, Alexandros Patsouras, Errika Voutyritsa, Athanasios Syllaios, Evangelos Koustas, Nikolaos Trakas, Dimitrios Dimitroulis
Summary: Triple-negative breast cancer is an aggressive subtype of breast cancer that does not respond well to hormone therapy but often shows good response to chemotherapy. It is important to investigate new beneficial targeted therapies in order to achieve enhanced outcomes for patients.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Ugur Sahin, Petra Oehm, Evelyna Derhovanessian, Robert A. Jabulowsky, Mathias Vormehr, Maike Gold, Daniel Maurus, Doreen Schwarck-Kokarakis, Andreas N. Kuhn, Tana Omokoko, Lena M. Kranz, Mustafa Diken, Sebastian Kreiter, Heinrich Haas, Sebastian Attig, Richard Rae, Katarina Cuk, Alexandra Kemmer-Brueck, Andrea Breitkreuz, Claudia Tolliver, Janina Caspar, Juliane Quinkhardt, Lisa Hebich, Malte Stein, Alexander Hohberger, Isabel Vogler, Inga Liebig, Stephanie Renken, Julian Sikorski, Melanie Leierer, Verena Mueller, Heidrun Mitzel-Rink, Matthias Miederer, Christoph Huber, Stephan Grabbe, Jochen Utikal, Andreas Pinter, Roland Kaufmann, Jessica C. Hassel, Carmen Loquai, Oezlem Tuereci
Article
Gastroenterology & Hepatology
Bernd Heinrich, Zachary J. Brown, Laurence P. Diggs, Mathias Vormehr, Chi Ma, Varun Subramanyam, Umberto Rosato, Benjamin Ruf, Juliane S. Walz, John C. McVey, Simon Wabitsch, Qiong Fu, Su Jong Yu, Qianfei Zhang, Chunwei W. Lai, Ugur Sahin, Tim F. Greten
Summary: This study found that steatohepatitis reduces infiltration of CD4(+) T cells and effector memory cells in liver tumors, which decreases the efficacy of immunotherapeutic agents like M30 and aOX40 in inhibiting tumor growth. N-acetylcysteine can restore T-cell numbers in tumors and enhance the ability of M30 and aOX40 to slow tumor growth in mice.
Correction
Multidisciplinary Sciences
Ugur Sahin, Alexander Muik, Evelyna Derhovanessian, Isabel Vogler, Lena M. Kranz, Mathias Vormehr, Alina Baum, Kristen Pascal, Jasmin Quandt, Daniel Maurus, Sebastian Brachtendorf, Verena Lorks, Julian Sikorski, Rolf Hilker, Dirk Becker, Ann-Kathrin Eller, Jan Grutzner, Carsten Boesler, Corinna Rosenbaum, Marie-Cristine Kuhnle, Ulrich Luxemburger, Alexandra Kemmer-Bruck, David Langer, Martin Bexon, Stefanie Bolte, Katalin Kariko, Tania Palanche, Boris Fischer, Armin Schultz, Pei-Yong Shi, Camila Fontes-Garfias, John L. Perez, Kena A. Swanson, Jakob Loschko, Ingrid L. Scully, Mark Cutler, Warren Kalina, Christos A. Kyratsous, David Cooper, Philip R. Dormitzer, Kathrin U. Jansen, Ozlem Tureci
Article
Multidisciplinary Sciences
Annette B. Vogel, Isis Kanevsky, Ye Che, Kena A. Swanson, Alexander Muik, Mathias Vormehr, Lena M. Kranz, Kerstin C. Walzer, Stephanie Hein, Alptekin Gueler, Jakob Loschko, Mohan S. Maddur, Ayuko Ota-Setlik, Kristin Tompkins, Journey Cole, Bonny G. Lui, Thomas Ziegenhals, Arianne Plaschke, David Eisel, Sarah C. Dany, Stephanie Fesser, Stephanie Erbar, Ferdia Bates, Diana Schneider, Bernadette Jesionek, Bianca Saenger, Ann-Kathrin Wallisch, Yvonne Feuchter, Hanna Junginger, Stefanie A. Krumm, Andre P. Heinen, Petra Adams-Quack, Julia Schlereth, Stefan Schille, Christoph Kroener, Ramon de la Caridad Guimil Garcia, Thomas Hiller, Leyla Fischer, Rani S. Sellers, Shambhunath Choudhary, Olga Gonzalez, Fulvia Vascotto, Matthew R. Gutman, Jane A. Fontenot, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil Han, Andreas A. H. Su, Joshua A. Lees, Nicole L. Nedoma, Ellene H. Mashalidis, Parag Sahasrabudhe, Charles Y. Tan, Danka Pavliakova, Guy Singh, Camila Fontes-Garfias, Michael Pride, Ingrid L. Scully, Tara Ciolino, Jennifer Obregon, Michal Gazi, Ricardo Carrion, Kendra J. Alfson, Warren Kalina, Deepak Kaushal, Pei-Yong Shi, Thorsten Klamp, Corinna Rosenbaum, Andreas N. Kuhn, Ozlem Tureci, Philip R. Dormitzer, Kathrin U. Jansen, Ugur Sahin
Summary: The two vaccine candidates, BNT162b1 and BNT162b2, developed contain modified messenger RNA encoding immunogens derived from the spike glycoprotein of SARS-CoV-2. They have shown promising immune responses in mice and rhesus macaques, with ongoing phase I trials in Germany and the USA and a global phase II/III trial for BNT162b2.
Article
Biochemical Research Methods
Franziska Lang, Pablo Riesgo Ferreiro, Martin Loewer, Ugur Sahin, Barbara Schroers
Summary: The study focused on detecting and predicting true neoantigens, leading to the development of an easy-to-use tool called NeoFox for annotating neoantigen candidates with 16 features.
Review
Biochemistry & Molecular Biology
Jan D. Beck, Daniel Reidenbach, Nadja Salomon, Ugur Sahin, Ozlem Tureci, Mathias Vormehr, Lena M. Kranz
Summary: Synthetic mRNA serves as a versatile template for protein synthesis and has a wide range of pharmaceutical applications, including cancer immunotherapy. Strategies such as stimulating pattern recognition receptors and nucleoside modification enhance the effectiveness and safety of mRNA vaccines.
Article
Biochemistry & Molecular Biology
Luisa Bresadola, David Weber, Christoph Ritzel, Martin Loewer, Valesca Bukur, Oezlem Akilli-Oeztuerk, Julia Becker, Hisham Mehanna, Barbara Schroers, Fulvia Vascotto, Ugur Sahin, Anthony Kong
Summary: This study analysed genomic and transcriptomic profiles of three synchronous primary malignancies and a recurrence, finding remarkable heterogeneity among the primary tumors. The origin of the recurrence was traced through shared mutation patterns, and the patient carried germline variants that may predispose to carcinogenesis, along with a history of alcohol and tobacco consumption. Immune cell infiltration analysis revealed an immunosuppressive environment in all samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Ugur Sahin, Alexander Muik, Isabel Vogler, Evelyna Derhovanessian, Lena M. Kranz, Mathias Vormehr, Jasmin Quandt, Nicole Bidmon, Alexander Ulges, Alina Baum, Kristen E. Pascal, Daniel Maurus, Sebastian Brachtendorf, Verena Loerks, Julian Sikorski, Peter Koch, Rolf Hilker, Dirk Becker, Ann-Kathrin Eller, Jan Gruetzner, Manuel Tonigold, Carsten Boesler, Corinna Rosenbaum, Ludwig Heesen, Marie-Cristine Kuhnle, Asaf Poran, Jesse Z. Dong, Ulrich Luxemburger, Alexandra Kemmer-Brueck, David Langer, Martin Bexon, Stefanie Bolte, Tania Palanche, Armin Schultz, Sybille Baumann, Azita J. Mahiny, Gabor Boros, Jonas Reinholz, Gabor T. Szabo, Katalin Kariko, Pei-Yong Shi, Camila Fontes-Garfias, John L. Perez, Mark Cutler, David Cooper, Christos A. Kyratsous, Philip R. Dormitzer, Kathrin U. Jansen, Oezlem Tuereci
Summary: The BNT162b2 vaccine shows 95% efficacy in preventing COVID-19 by boosting neutralizing antibody titres and activating specific T cell responses. The vaccine-induced immune response is broad and stable, lasting for a prolonged period, providing good coverage against various SARS-CoV-2 variants.
Review
Biotechnology & Applied Microbiology
Franziska Lang, Barbara Schroers, Martin Loewer, Oezlem Tuereci, Ugur Sahin
Summary: This Review discusses the use of tumor-specific neoantigens in anticancer vaccines and introduces the mechanisms of neoantigen T cell recognition, as well as computational approaches to predict which neoantigens might confer proficient antitumor immunity in patients. Individualized treatment approaches are required to harness the full potential of the unique cancer mutations in each patient. Computational algorithms and machine-learning tools can be used to identify mutations, prioritize T cell-recognized antigens, and design personalized vaccines for each patient.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Multidisciplinary Sciences
Barbara Schrors, Pablo Riesgo-Ferreiro, Patrick Sorn, Ranganath Gudimella, Thomas Bukur, Thomas Rosler, Martin Lower, Ugur Sahin
Summary: Research has shown that SARS-CoV-2 spike protein exhibits mutations, with the majority being recurrent variants. While most spike protein mutants have low mutation rates, some variants may impact antibody binding or T-cell recognition. Additionally, high-confidence subclonal variants were identified in around 2.6% of NGS datasets, indicating potential co-infections with various strains and intra-host evolution.
Article
Biotechnology & Applied Microbiology
David Weber, Jonas Ibn-Salem, Patrick Sorn, Martin Suchan, Christoph Holtstraeter, Urs Lahrmann, Isabel Vogler, Kathrin Schmoldt, Franziska Lang, Barbara Schroers, Martin Loewer, Ugur Sahin
Summary: EasyFuse is a machine learning computational pipeline that accurately and sensitively detects personal gene fusions from transcriptome data in cancer samples, and it has been proven in immunogenicity testing that personal gene fusions are important in personalized immunotherapy.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Leonard Kaps, Anne Huppertsberg, Niklas Choteschovsky, Adrian Klefenz, Feyza Durak, Babara Schroers, Mustafa Diken, Emma Eichler, Sebastian Rosigkeit, Sascha Schmitt, Christian Leps, Alicia Schulze, Friedrich Foerster, Ernesto Bockamp, Bruno G. De Geest, Kaloian Koynov, Hans-Joachim Raeder, Stefan Tenzer, Federico Marini, Detlef Schuppan, Lutz Nuhn
Summary: In this study, liver fibrosis progression was prevented by repolarizing M2-type macrophages towards a non-fibrotic phenotype using a pH-degradable nanogel carrier system. The nanogels efficiently delivered the drug alendronate to nonparenchymal cells of fibrotic livers, reprogramming profibrotic M2 into antifibrotic M1 macrophages and preventing liver fibrosis progression. This approach has potential implications for the treatment of diseases driven by M2-type macrophages, including cancer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Jian Wang, Tobias Weiss, Marian C. Neidert, Nora C. Toussaint, Reza Naghavian, Carla Selles Moreno, Magdalena Foege, Paula Tomas Ojer, Gioele Medici, Ivan Jelcic, Daniel Schulz, Elisabeth Rushing, Susanne Dettwiler, Barbara Schrors, Joo Heon Shin, Ron McKay, Catherine J. Wu, Andreas Lutterotti, Mireia Sospedra, Holger Moch, Erich F. Greiner, Bernd Bodenmiller, Luca Regli, Michael Weller, Patrick Roth, Roland Martin
Summary: The study developed a strategy to design neopeptides with enhanced immunogenicity through single amino acid mutations. Vaccination with these peptides resulted in immune responses from CD8+ T cells and CD4+ T cells upon tumor recurrence.
CLINICAL CANCER RESEARCH
(2022)
Article
Virology
Thomas Bukur, Pablo Riesgo-Ferreiro, Patrick Sorn, Ranganath Gudimella, Johannes Hausmann, Thomas Roesler, Martin Loewer, Barbara Schroers, Ugur Sahin
Summary: CoVigator is a tool for monitoring SARS-CoV-2 mutations, providing a knowledge base, variant calling, and an interactive dashboard. It can identify and track virus mutations, offering the largest dataset on SARS-CoV-2 intrahost mutations and is available for download.
Article
Immunology
Barbara Schroers, Brett J. Hos, Ikra G. Yildiz, Martin Loewer, Franziska Lang, Christoph Holtstraeter, Julia Becker, Mathias Vormehr, Ugur Sahin, Ferry Ossendorp, Mustafa Diken
Summary: The MC38 cell line, commonly used for colorectal carcinoma studies, has two sub-cell lines (MC38-K and MC38-L) with distinct genomic and transcriptomic differences. CD8+ T cell recognition also varies between the two sub-cell lines. This highlights the importance of accurately selecting the appropriate sub-cell line for research.
FRONTIERS IN IMMUNOLOGY
(2023)