Article
Multidisciplinary Sciences
Enrique J. Arenas, Alex Martinez-Sabadell, Irene Rius Ruiz, Macarena Roman Alonso, Marta Escorihuela, Antonio Luque, Carlos Alberto Fajardo, Alena Gros, Christian Klein, Joaquin Arribas
Summary: Immunotherapy has shown promise in cancer treatment, with T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) being potential tools for this approach. This study reveals that disruption of interferon-gamma signaling, including downregulation of JAK2, in cancer cells confers resistance to T cell-mediated cytotoxicity directed against HER2, highlighting a potential mechanism for resistance to T cell-engaging therapies.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Aleksandra Rodak, Gerhard Stadlmayr, Katharina Stadlbauer, Dominic Lichtscheidl, Madhusudhan Reddy Bobbili, Florian Rueker, Gordana Wozniak-Knopp
Summary: The study of IgE is important in the treatment of allergies and asthma, and therapeutic anti-IgE antibodies can intervene in its function by different mechanisms to reduce serum IgE levels. Bispecific antibody fusion proteins have shown promising results in eliciting cytotoxic T-cell-mediated killing through specific activation.
Article
Immunology
Ryan D. D. Molony, Theresa Funk, Gina Trabucco, Erik Corcoran, David Ruddy, Malini Varadarajan, GiNell Elliot, Michelle Piquet, Joni Lam, Matthew J. J. Meyer, Hui Qin Wang, Sema Kurtulus, Haihui Lu
Summary: CD3-engaging bispecific antibodies (BsAbs) enable killing of target cells by forming an immune synapse between T cells and tumor cells, without relying on preexisting tumor specific T cell receptor. It has been found that CD8+ T cells depend on signaling factors derived from CD4+ T cells to achieve sustained killing. The mammalian target of rapamycin (mTOR) pathway and other candidate genes have been identified as intrinsic regulators of BsAb-induced T cell proliferation and/or activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ewa Kubicka, Lawrence G. Lum, Manley Huang, Archana Thakur
Summary: The study demonstrates that arming activated T cells (ATCs) with bispecific antibodies (BiAbs) can effectively target and lyse acute myeloid leukemia (AML) cells and leukemic stem cells (LSCs), providing a potent and non-toxic therapeutic strategy to enhance chemo-responsiveness in older patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Congcong Zhang, Jasmin Roeder, Anne Scherer, Malena Bodden, Jordi Pfeifer Serrahima, Anita Bhatti, Anja Waldmann, Nina Mueller, Pranav Oberoi, Winfried S. Wels
Summary: The study developed a bispecific antibody NKAB-ErbB2 that redirects NKG2D-expressing effector cells to ErbB2-positive tumor cells, synergizing with NKG2D-CAR cells and natural NK cell-mediated cytotoxicity. In mouse model, NKAR-NK-92 cells combined with NKAB-ErbB2 effectively suppressed tumor outgrowth and induced antitumor immunity and cures in most animals.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Karsten M. Warwas, Marten Meyer, Marcia Goncalves, Gerhard Moldenhauer, Nadja Bulbuc, Susanne Knabe, Claudia Luckner-Minden, Claudia Ziegelmeier, Claus Peter Heussel, Inka Zoernig, Dirk Jaeger, Frank Momburg
Summary: This study demonstrates that co-stimulation significantly enhances the tumoricidal activity of T cell-activating BiMAb, while reducing the required dose for T cell activation and overcoming immune-suppressive effects. Co-stimulation could provide a more localized and effective activation of the immune system against tumor cells, showing promise for cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Daniele Caracciolo, Caterina Riillo, Andrea Ballerini, Giuseppe Gaipa, Ludovic Lhermitte, Marco Rossi, Cirino Botta, Eugenie Duroyon, Katia Grillone, Maria Eugenia Gallo Cantafio, Chiara Buracchi, Greta Alampi, Alessandro Gulino, Beatrice Belmonte, Francesco Conforti, Gaetanina Golino, Giada Juli, Emanuela Altomare, Nicoletta Polera, Francesca Scionti, Mariamena Arbitrio, Michelangelo Iannone, Massimo Martino, Pierpaolo Correale, Gabriella Talarico, Andrea Ghelli Luserna di Rora, Anna Ferrari, Daniela Concolino, Simona Sestito, Licia Pensabene, Antonio Giordano, Markus Hildinger, Maria Teresa Di Martino, Giovanni Martinelli, Claudio Tripodo, Vahid Asnafi, Andrea Biondi, Pierosandro Tagliaferri, Pierfrancesco Tassone
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate, lacking effective immune-therapeutics. In this study, an afucosylated monoclonal antibody and two bispecific T-cell engagers targeting UMG1 on T-ALL cells were developed and shown to have high killing activity. These findings provide a potential clinical development for innovative immune-therapeutics for T-ALL.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Daniel Klewinghaus, Lukas Pekar, Paul Arras, Simon Krah, Bernhard Valldorf, Harald Kolmar, Stefan Zielonka
Summary: In this study, we engineered bispecific ultralong CDR-H3 common light chain antibodies derived from cattle and demonstrated their potential for various biotechnological applications.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Ajit Singh, Sundee Dees, Iqbal S. Grewal
Summary: Bispecific antibodies redirecting CD3+ T cells to target tumors hold promise as an immunotherapeutic strategy. Despite early success, challenges such as recruiting counterproductive T cell subsets, systemic cytokine release, immune checkpoint molecule expansion, and an immunosuppressive tumor microenvironment need to be overcome for optimal clinical benefit.
BRITISH JOURNAL OF CANCER
(2021)
Article
Immunology
Yi Wang, Yuxi Zhang, Haoyi Sun, Jilan Chen, Hui Yang, Zhanqiong Zhong, Xiaoqian Xiao, Yanping Li, Yibei Tang, Haolan Lu, Xinzhi Tang, Mengyang Zhang, Wenjun Wu, Shiyi Zhou, Jiahui Yang
Summary: Over the last decade, immuno-oncologic drugs, particularly CD3-engaging bispecific antibodies (biAbs), have seen rapid development. However, there are still significant challenges in their clinical development for solid tumors, especially non-small cell lung cancer (NSCLC). In this study, a ROR1 x CD3 biAb, called R11 x v9 biAb, was investigated for its tumor-inhibiting role in NSCLC. The biAb demonstrated specific binding to T cells and tumor cells, dose-dependent cytotoxicity against various ROR1+ NSCLC cell lines, and promoted immune responses in tumor tissues. The antitumor activity of R11 x v9 biAb was confirmed in mouse models of ROR1+ NSCLC without observed side effects, supporting further preclinical and clinical studies.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Hematology
Lindsay Hammons, Shabi Haider, Andrew J. Portuguese, Rahul Banerjee, Aniko Szabo, Marcelo Pasquini, Saurabh Chhabra, Sabarinath Radhakrishnan, Meera Mohan, Ravi Narra, Jing Dong, Siegfried Janz, Nirav N. Shah, Mehdi Hamadani, Anita D'Souza, Parameswaran Hari, Binod Dhakal
Summary: CAR-T and BsAb therapies are feasible, safe, and provide deep and durable responses in MM patients with a prior history of allo-HCT.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Jeong A. Park, Madelyn Espinosa-Cotton, Hong-fen Guo, Sebastien Monette, Nai-Kong Cheung
Summary: This study demonstrates that using anti-VEGF antibodies can significantly improve the therapeutic efficacy of T cell immunotherapies by increasing HEVs and promoting the infiltration of cytotoxic CD8(+) TILs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Pharmacology & Pharmacy
Timothy Qi, Xiaozhi Liao, Yanguang Cao
Summary: Bispecific T cell engagers (bsTCEs) have shown promise as cancer immunotherapy drugs, but face challenges in clinical development. Quantitative systems pharmacology (QSP) can be a powerful tool to overcome these challenges, providing a deeper understanding of pharmacology, guiding dose selection, and improving treatment outcomes.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Patricia Himmels, Thi Thu Thao Nguyen, Maresa Caunt Mitzner, Alfonso Arrazate, Stacey Yeung, Jeremy Burton, Robyn Clark, Klara Totpal, Raj Jesudason, Angela Yang, Margaret Solon, Jeffrey Eastham, Zora Modrusan, Joshua D. Webster, Amy A. Lo, Robert Piskol, Weilan Ye
Summary: Preclinical and clinical studies show that T cell-dependent bispecific antibodies (TDBs) not only kill tumors but also cause systemic changes, leading to adverse events. In this study, the acute responses to TDBs in tumor-bearing mice were characterized in detail. The results reveal rapid and significant accumulation of lymphocytes and activation of endothelial cells (ECs) around large blood vessels in normal organs, particularly the liver. It is suggested that differential responses in normal tissues and tumors may be attributed to organ-specific ECs, and a list of genes selectively upregulated in large liver vessels by TDBs is identified. Furthermore, the study demonstrates that CD9 facilitates the interaction between T cells and ECs through the support of ICAM-1 in response to soluble factors released from TDB-mediated cytotoxic reactions. These findings provide insights into the response of different vascular beds to cancer immunotherapy and may contribute to improving their safety and efficacy.
Article
Oncology
Nanna Skeltved, Mie A. A. Nordmaj, Nicolai T. T. Berendtsen, Robert Dagil, Emilie M. R. Stormer, Nader Al-Nakouzi, Ke Jiang, Alexandra Aicher, Christopher Heeschen, Tobias Gustavsson, Swati Choudhary, Ismail Gogenur, Jan P. P. Christensen, Thor G. G. Theander, Mads Daugaard, Ali Salanti, Morten A. A. Nielsen
Summary: The malaria protein VAR2CSA has anti-tumor efficacy by binding to oncofetal chondroitin sulfate (ofCS). Combining V-aCD3 with an immune checkpoint inhibitor enhances the anti-tumor effects, leading to complete elimination of solid tumors in mice.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Immunology
Kathleen M. E. Gallagher, Mark B. Leick, Rebecca C. Larson, Trisha R. Berger, Katelin Katsis, Jennifer Y. Yam, Marcela Maus
Summary: Breakthrough cases among vaccinated individuals highlight the importance of long-term immunity against SARS-CoV-2 and its variants. Antibody levels and anti-spike T-cell responses decrease over time and are lower in those vaccinated with BNT162b2 compared to mRNA-1273. T-cell responses to variants remain relatively unaffected.
CLINICAL INFECTIOUS DISEASES
(2022)
Letter
Oncology
Joan How, Kathleen M. E. Gallagher, Yiwen Liu, Katelin Katsis, Eva L. Elder, Rebecca C. Larson, Mark B. Leick, Donna Neuberg, Marcela V. Maus, Gabriela S. Hobbs
Article
Multidisciplinary Sciences
Julia Joung, Paul C. Kirchgatterer, Ankita Singh, Jang H. Cho, Suchita P. Nety, Rebecca C. Larson, Rhiannon K. Macrae, Rebecca Deasy, Yuen-Yi Tseng, Marcela Maus, Feng Zhang
Summary: This study identifies several genes associated with tumor resistance to T cell cytotoxicity through a genome-scale CRISPR activation screen. Overexpression of these candidate genes, including MCL1, JUNB, and B3GNT2, confers resistance to T cell killing in various cancer cell types and mouse xenografts. Mechanistically, MCL1 and JUNB modulate the mitochondrial apoptosis pathway, while B3GNT2 disrupts interactions between tumor and T cells, leading to reduced T cell activation. Inhibition of these candidate genes sensitizes tumor models to T cell cytotoxicity.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Hematology
Marcela Maus
Summary: Genetically modified immune effector cells (IECs) hold promise as a new type of therapeutic for hematologic malignancies, but their potential to increase the risk of secondary cancers is unclear. This study found no increased risk of secondary cancers in over 1000 patient-years of follow-up across multiple clinical trials of genetically modified IECs for cancer.
Editorial Material
Oncology
Mahmoud R. Gaballa, Marcela Maus
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Kimberly R. Hagel, Rand Arafeh, Sydney Gang, Taylor E. Arnoff, Rebecca C. Larson, John G. Doench, Nathan D. Mathewson, Kai W. Wucherpfennig, Marcela Maus, William C. Hahn
Summary: This study uncovers multiple antigen-dependent and independent mechanisms of CAR T-cell evasion by pancreatic cancer, including the loss of genes involved in GPI-anchor biosynthesis and attachment pathway and genes that regulate tumor transcriptional responses. The identification of these resistance mechanisms provides insights into the landscape of tumor cell intrinsic resistance and potential approaches to improve CAR T-cell therapy efficacy in pancreatic cancer.
Review
Multidisciplinary Sciences
Darrell J. Irvine, Marcela V. Maus, David J. Mooney, Wilson W. Wong
Summary: Immune cell therapy is a promising approach to treating diseases, especially cancer, by engineering immune cells to recognize and respond to specific conditions. This therapy has already been approved for clinical use and continues to be developed and tested in various applications.
News Item
Biochemistry & Molecular Biology
Zachariah DeFilipp, Marcela V. Maus
Summary: The composition of the intestinal microbiome can predict clinical outcomes of CAR-T cell therapy for lymphoma, informing microbiota-based interventions.
Editorial Material
Oncology
Mark B. B. Leick, Marcela V. V. Maus
Summary: Plasma cell-free DNA analysis is an effective liquid biopsy for evaluating circulating tumor DNA in cancer treatment. A recent study shows that cell-free DNA can also provide information on expansion kinetics and tumor-infiltration patterns in patients receiving chimeric antigen receptor T cells. Together with circulating tumor DNA, it offers valuable prognostic insights into intratumoral dynamics.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Alexandra L. Pourzia, Michael L. Olson, Stefanie R. Bailey, Angela C. Boroughs, Aditi Aryal, Jeremy Ryan, Marcela V. Maus, Anthony Letai
CELL DEATH & DISEASE
(2023)
Review
Immunology
Marie-Noelle Kronig, Marc Wehrli, Diego Salas-Benito, Marcela V. Maus
Summary: Digestive tract cancers, especially pancreatic cancer, have high incidence, prevalence, and mortality rates, and current immunotherapy options are limited. Cellular immunotherapy, specifically CAR T-cell therapy, has shown promising results in hematological malignancies and there is interest in translating this success to solid malignancies such as DTC. This review focuses on the advances and hurdles of CAR T-cell therapy in DTC.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biotechnology & Applied Microbiology
Magdi Elsallab, Marcela V. Maus
Summary: Chimeric antigen receptor (CAR) T cells are revolutionizing the treatment of hematological malignancies. The current autologous and central manufacturing approach presents challenges in meeting the growing demand. Distributed manufacturing with advanced technologies is crucial to increase capacity and ensure uniform product quality. Expanded role of accreditation bodies and regulatory amendments are also necessary to support this model.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yi Lin, Noopur S. Raje, Jesus G. Berdeja, David S. Siegel, Sundar Jagannath, Deepu Madduri, Michaela Liedtke, Jacalyn Rosenblatt, Marcela V. Maus, Monica Massaro, Fabio Petrocca, Ashish Yeri, Olivia Finney, Andrea Caia, Zhihong Yang, Nathan Martin, Timothy B. Campbell, Julie Rytlewski, Jaymes Fuller, Kristen Hege, Nikhil C. Munshi, James N. Kochenderfer
Summary: This study conducted a post hoc analysis of the use of Idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma and found that it is safe and well-tolerated, with a positive impact on response rates. Additionally, the study identified a correlation between the state of T cells and durable responses.
Review
Biotechnology & Applied Microbiology
Marco Ruella, Felix Korell, Patrizia Porazzi, Marcela V. Maus
Summary: Chimeric antigen receptor (CAR)-T cells have shown great potential in treating blood cancers, but resistance to this therapy remains a challenge. This review summarizes the mechanisms of resistance to CAR-T cell immunotherapy, including CAR-T cell dysfunction, tumor resistance, and the immunosuppressive tumor microenvironment. It also discusses current research strategies to overcome these resistance mechanisms.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Hematology
Akshay Sharma, Stephanie Farnia, Folashade Otegbeye, Amy Rinkle, Jugna Shah, Nirali N. Shah, Saar Gill, Marcela V. Maus
Summary: As cellular and genetic therapies move from theory to practice, it has become clear that there are conflicting and imprecise terminologies to describe these novel therapeutic products. Standardization of the nomenclature is crucial for regulatory framework, training programs, accessibility decisions, and reimbursement consistency.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
