Review
Immunology
Manasi P. Jogalekar, Ramya Lakshmi Rajendran, Fatima Khan, Crismita Dmello, Prakash Gangadaran, Byeong-Cheol Ahn
Summary: CAR-T cell therapy is a promising immune cell therapy for cancer, showing remarkable clinical responses in B-cell leukemia or lymphoma. However, it still faces challenges in treating other hematological and solid tumor malignancies, including severe toxicities and limited anti-tumor efficacy. This review discusses innovative CAR T-cell strategies to improve treatment outcomes and addresses the current challenges and new developments in CAR T-cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Yifan Xu, Jin Jiang, Yutong Wang, Wei Wang, Haokun Li, Wenyu Lai, Zhipeng Zhou, Wei Zhu, Zheng Xiang, Zhiming Wang, Zhe Zhu, Lingfeng Yu, Xiaolan Huang, Hua Zheng, Sha Wu
Summary: Gynecologic malignancies are leading causes of death among women worldwide, and adoptive T cell therapy using engineered T cells has shown promising efficacy in treating tumors. Ongoing research is driving the application of this therapy in the treatment of gynecologic malignancies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Manish Malviya, Zita E. H. Aretz, Zaki Molvi, Jayop Lee, Stephanie Pierre, Patrick Wallisch, Tao Dao, David A. Scheinberg
Summary: Recent advances in discovering and engineering therapeutic T-cell receptors (TCRs) or TCR antibody mimics lag behind therapeutic antibodies, but hold great promise for treating various medical conditions, particularly cancers. TCR-based agents, including engineered cells, soluble TCRs, TCR-mimic antibodies, and TCR-based CAR T cells, offer the potential for highly specific drugs that can target intracellular antigens inaccessible to traditional antibodies. However, there are challenges to overcome in terms of discovery, specificity, pharmacokinetics, and optimal modality of use. HLA restriction and off-target reactivities also present barriers to widespread development and use of TCR-based agents.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Medicine, Research & Experimental
Haixia Li, Dani Zhong, Huiguan Luo, Wei Shi, Shenxia Xie, Hangbiao Qiang, Lichen Zhu, Li Gao, Jun Liu, Shuyang Sun, Ziqiang Ding, Xiaomei Yang, Xiaoling Lu
Summary: Chimeric antigen receptor (CAR) T-cell immunotherapy is a research hotspot in the field of malignant tumor treatment. This study investigates whether nanobody-based T cell receptor-like CAR T cells can target intracellular antigens and effectively kill tumor cells. By developing HLA-A2/GPC3 and HLA-A2/WT1-specific nanobodies and incorporating them into TCR-like CARs, the researchers found that these CAR-redirected T cells could selectively recognize and kill MHC/peptide complex-expressing tumor cells both in vitro and in mouse tumor models. This study offers a potential strategy to target intracellular antigens and expand the application of CAR T-cell therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Immunology
Paul Shafer, Lauren M. Kelly, Valentina Hoyos
Summary: This article presents a review of the use of engineered T cells for cancer therapy. The mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs are discussed, along with the current classes of cancer antigens recognized by TCR T therapies and pre-clinical strategies for TCR discovery and enhancement. The current landscape of clinical trials for TCR T therapy is also reviewed, providing insights into the development of future engineered TCR approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Xiaomin Zhang, Lingling Zhu, Hui Zhang, Shanshan Chen, Yang Xiao
Summary: CAR-T cell therapy has shown significant success in the treatment of hematological malignancies, but challenges remain in terms of adverse events and resistance mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Hongtao Liu, Chongxian Pan, Wenru Song, Delong Liu, Zihai Li, Lei Zheng
Summary: Cell therapy has advanced rapidly in recent years, with applications expanding beyond hematologic malignancies to solid tumors, targeting personalized tumor-specific neoantigens and enhancing T cell trafficking. Despite challenges, the maturation of technologies in T cell engineering is expected to lead a revolution in cancer immunotherapy in the near future.
BIOMARKER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Lusine Hovhannisyan, Carsten Riether, Daniel M. Aebersold, Michaela Medova, Yitzhak Zimmer
Summary: CAR T cell-based therapies have revolutionized the treatment of hematological malignancies. However, the treatment of solid tumors with CAR T cells remains challenging. Radiation therapy, in combination with immune checkpoint inhibitors, has shown promising results in clinical trials. Combining radiation therapy with CAR T cell therapy may overcome the limitations in solid tumor treatment. This review discusses the potential and risks of this combination in cancer patients.
Article
Oncology
Jiali Cheng, Yuyan Zhao, Hui Hu, Ling Tang, Yuhao Zeng, Xinyue Deng, Shengnan Ding, An-Yuan Guo, Qing Li, Xiaojian Zhu
Summary: This study demonstrates that knocking out the CD70 gene in T-cells can prevent early exhaustion of CAR-70 T-cells and improve the quality and anti-tumor capability of CAR T-cells targeting self-expressed antigens.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Immunology
Wenshuai Li, Xuanxuan Pan, Lirong Chen, Haoshu Cui, Shaocong Mo, Yida Pan, Yuru Shen, Menglin Shi, Jianlin Wu, Feifei Luo, Jie Liu, Na Li
Summary: Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has shown remarkable efficacy against hematological malignancies, but its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME) can lead to T cell exhaustion and compromise the efficacy of CAR-T cells. This review discusses the metabolic characteristics of T cells and potential metabolic approaches to improve the efficacy and persistence of CAR-T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Frederik Holm Rothemejer, Nanna Pi Lauritsen, Ole Schmeltz Sogaard, Martin Tolstrup
Summary: This article reviews the challenges and potential strategies in designing CAR T cells against HIV and other chronic viral infections. It emphasizes the importance of CAR T cell persistence and efficacy, which is dependent on antigen density and target cell abundance.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Anqi Ren, Xiqin Tong, Na Xu, Tongcun Zhang, Fuling Zhou, Haichuan Zhu
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with high relapse rates and poor prognosis. Current guidelines do not recommend specific treatments, and allogeneic stem cell transplant is the only curative therapy with potential risks. Recent trials have shown success in treating hematologic malignancies with immunotherapies such as monoclonal antibodies, checkpoint inhibitors, and CAR T therapies. However, developing CAR T immunotherapy for T-ALL is challenging due to potential risks of fratricide, T-cell aplasia, immunosuppression, and product contamination.
Review
Immunology
Sun Il Choi, Jinlong Yin
Summary: Glioblastoma (GBM) is the most common malignant brain tumor, and alternative tumor-specific therapies are urgently needed. Chimeric antigen receptor (CAR) T cell therapy shows promise for hematological malignancies, but its effectiveness for solid tumors, especially GBM, needs improvement. This review discusses strategies for enhancing CAR T cell effectiveness in GBM treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Hematology
Rawan G. Faram, Marco L. Davila
Summary: The CAR-HEMATOTOX predictive model by Rejeski et al in this issue of Blood can identify patients at highest risk of hematologic toxicity following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory large B-cell lymphoma.
Review
Immunology
Michael Hiltensperger, Angela M. Krackhardt
Summary: Adoptive cell therapy (ACT) has witnessed a surge in new therapeutic approaches, particularly with the recent approvals of CAR-T cell therapies. The focus of ACT is to genetically modify T cells to target and kill tumor cells. Both CAR-T cells and TCR-T cells have advantages and limitations in targeting solid tumors. Next-generation CAR-T cells and genetically engineered TCR-T cells targeting intracellular antigens might address these challenges. Ongoing clinical trials, current challenges, and future directions in this field are also discussed.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Gastroenterology & Hepatology
Antonio Bertoletti, Carolina Boni
Article
Multidisciplinary Sciences
Leo Swadling, Mariana O. Diniz, Nathalie M. Schmidt, Oliver E. Amin, Aneesh Chandran, Emily Shaw, Corinna Pade, Joseph M. Gibbons, Nina Le Bert, Anthony T. Tan, Anna Jeffery-Smith, Cedric C. S. Tan, Christine Y. L. Tham, Stephanie Kucykowicz, Gloryanne Aidoo-Micah, Joshua Rosenheim, Jessica Davies, Marina Johnson, Melanie P. Jensen, George Joy, Laura E. McCoy, Ana M. Valdes, Benjamin M. Chain, David Goldblatt, Daniel M. Altmann, Rosemary J. Boyton, Charlotte Manisty, Thomas A. Treibel, James C. Moon, Lucy van Dorp, Francois Balloux, Aine McKnight, Mahdad Noursadeghi, Antonio Bertoletti, Mala K. Maini
Summary: Research suggests that some individuals can clear potential SARS-CoV-2 infection after exposure, with T cells playing a role in the process. Studying healthcare workers who tested negative for antibodies revealed that they had stronger and more diverse memory T cells, with a focus on RTC.
Letter
Hematology
Bernice Ling Zhi Oh, Nicole Tan, Ruklanthi de Alwis, Kamini Kunasegaran, Zhiwei Chen, Michelle Poon, Esther Chan, Jenny G. H. Low, Allen Eng Juh Yeoh, Antonio Bertoletti, Nina Le Bert
Editorial Material
Gastroenterology & Hepatology
Antonio Bertoletti
JOURNAL OF HEPATOLOGY
(2022)
Article
Immunology
Joey Ming Er Lim, Anthony Tanoto Tan, Nina Le Bert, Shou Kit Hang, Jenny Guek Hong Low, Antonio Bertoletti
Summary: Nasal-resident T cells specific for SARS-CoV-2 were detected in vaccinated individuals only after infection, highlighting the significance of nasal challenge in the formation of antiviral immunity at the site of infection.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Immunology
Antonio Bertoletti, Nina Le Bert, Anthony T. Tan
Summary: This review summarizes the evidence supporting the role of SARS-CoV-2-specific T cells in disease protection and analyzes the different factors that may influence the magnitude, function, and anatomical localization of these T cells, as well as their impact on protecting the host from severe COVID-19 development.
Review
Biochemistry & Molecular Biology
Antonio Bertoletti, Nina Le Bert, Anthony T. Tan
Summary: The emergence of new SARS-CoV-2 lineages that can escape antibodies has reduced the protection provided by Spike-specific antibodies. As a result, T cells have taken on a more central role in containing viral replication and spread.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Joey Ming Er Lim, Shou Kit Hang, Smrithi Hariharaputran, Adeline Chia, Nicole Tan, Eng Sing Lee, Edwin Chng, Poh Lian Lim, Barnaby E. Young, David Chien Lye, Nina Le Bert, Antonio Bertoletti, Anthony T. Tan
Summary: This study compares the T cell responses in individuals vaccinated with inactivated SARS-CoV-2 or mRNA vaccines. Compared to mRNA vaccines, inactivated vaccines induce a lower magnitude of spike-specific T cell response, but the combination of other protein-specific T cell responses is quantitatively comparable to the spike-specific T cell response induced by mRNA vaccines and can efficiently tolerate the mutations of the Omicron lineage. However, this multi-protein-specific T cell response is primarily mediated by selective priming of CD4 T cells rather than coordinated expansion of CD4 and CD8 T cells.
CELL REPORTS MEDICINE
(2022)
Editorial Material
Gastroenterology & Hepatology
Antonio Bertoletti, Nina Le Bert
Letter
Gastroenterology & Hepatology
Antonio Bertoletti, Nina Le Bert, Anthony T. Tan, Carolina Boni, Paola Fisicaro, Carlo Ferrari, Kyong-Mi Chang, Adam J. Gehring, Georg Lauer, Mala Maini, Robert Thimme, Christoph Neumann-Haefelin
JOURNAL OF HEPATOLOGY
(2023)
Article
Immunology
Meiyin Lin, Sebastian Chakrit Bhakdi, Damien Tan, Joycelyn Jie Xin Lee, David Wai Meng Tai, Andrea Pavesi, Lu-En Wai, Tina Wang, Antonio Bertoletti, Anthony Tanoto Tan
Summary: This study developed a microscopy-based assay to quantify circulating tumor cells (CTCs) and demonstrated that IDRA HBV-TCR T cells can lyse free-floating HBV-HCC cells in whole blood in the presence of immunosuppressive drugs.
IMMUNOTHERAPY ADVANCES
(2023)
Article
Virology
Anthony T. Tan, Joey Ming Er Lim, Antonio Bertoletti
Article
Gastroenterology & Hepatology
Anthony Tanoto Tan, Fanping Meng, Jiehua Jin, Ji-Yuan Zhang, Si-Yu Wang, Lei Shi, Ming Shi, Yuanyuan Li, Yunbo Xie, Li-Min Liu, Chun-Bao Zhou, Alicia Chua, Zi Zong Ho, Junqing Luan, Jinfang Zhao, Jing Li, Lu-En Wai, Sarene Koh, Tingting Wang, Antonio Bertoletti, Fu-Sheng Wang
Summary: The study demonstrates the feasibility of using messenger RNA HBV-TCR-redirected T cells for treating patients with HBV-HCC, resulting in long-term clinical benefits. However, further validation is needed to assess the reliability and longevity of immune monitoring.
HEPATOLOGY COMMUNICATIONS
(2022)
