Article
Immunology
Zilong Guo, Yirui Zhang, Mingpeng Fu, Liang Zhao, Zhen Wang, Zhuoshuo Xu, Huifen Zhu, Xiaoli Lan, Guanxin Shen, Yong He, Ping Lei
Summary: The transferrin receptor (TfR) is being evaluated as an alternative target for CAR T cell therapy, showing potent cytotoxic effects against hematological malignancies. This suggests TfR could potentially broaden and enhance the therapeutic efficacy of CAR T cells, making it a promising universal target for further research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
J. Joseph Melenhorst, Gregory M. Chen, Meng Wang, David L. Porter, Changya Chen, McKensie A. Collins, Peng Gao, Shovik Bandyopadhyay, Hongxing Sun, Ziran Zhao, Stefan Lundh, Iulian Pruteanu-Malinici, Christopher L. Nobles, Sayantan Maji, Noelle Frey, Saar Gill, Lifeng Tian, Irina Kulikovskaya, Minnal Gupta, David E. Ambrose, Megan M. Davis, Joseph A. Fraietta, Jennifer L. Brogdon, Regina M. Young, Anne Chew, Bruce L. Levine, Donald L. Siegel, Cecile Alanio, E. John Wherry, Frederic D. Bushman, Simon F. Lacey, Kai Tan, Carl H. June
Summary: CAR T cells redirected to target CD19 demonstrated long-lasting potential and clonal stability in two patients with chronic lymphocytic leukaemia. Highly activated CD4(+) cells emerged and dominated the CAR T cell population at later time points. These unexpected CAR T cell populations provide novel insights into anti-cancer response and long-term remission in leukaemia.
Article
Hematology
Kai Rejeski, Ariel Perez, Pierre Sesques, Eva Hoster, Carolina Berger, Liv Jentzsch, Dimitrios Mougiakakos, Lisa Froelich, Josephine Ackermann, Veit Buecklein, Viktoria Blumenberg, Christian Schmidt, Laurent Jallades, Boris Fehse, Christoph Faul, Philipp Karschnia, Oliver Weigert, Martin Dreyling, Frederick L. Locke, Michael von Bergwelt-Baildon, Andreas Mackensen, Wolfgang Bethge, Francis Ayuk, Emmanuel Bachy, Gilles Salles, Michael D. Jain, Marion Subklewe
Summary: Hematotoxicity is a common adverse event in CAR T-cell therapy, with baseline thrombocytopenia and hyperferritinemia being significant predictive markers. The CAR-HEMATOTOX model can accurately predict the occurrence of severe neutropenia.
Review
Oncology
Hui Lu, Xiaoyan Zhao, Ziying Li, Yu Hu, Huafang Wang
Summary: The approval of CD19 CAR-engineered T cell products in B-cell malignancies is a breakthrough in CAR-T cell immunotherapy. However, limitations such as GVHD and other adverse effects restrict their wider applications. CAR-NK cells, with their unique characteristics, are considered promising candidates for cellular immunotherapy, offering potential off-the-shelf products for immediate clinical use without HLA-matching restrictions. Researchers are shifting focus from CAR-T cells to CAR-NK cells, discussing their advantages and challenges in clinical applications.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Malgorzata Bajor, Agnieszka Graczyk-Jarzynka, Katsiaryna Marhelava, Anna Burdzinska, Angelika Muchowicz, Agnieszka Goral, Andriy Zhylko, Karolina Soroczynska, Kuba Retecki, Marta Krawczyk, Marta Klopotowska, Zofia Pilch, Leszek Paczek, Karl-Johan Malmberg, Sebastien Walchli, Magdalena Winiarska, Radoslaw Zagozdzon
Summary: This study provides new information on the efficacy of PD-L1-targeted CAR against PD-L1(low) targets. The results show that PD-L1-CAR cells have strong reactivity and cytotoxicity against both PD-L1(high) and PD-L1(low) target cells. Additionally, PD-L1-CAR cells also exhibit potent cytotoxic effects against non-malignant cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Ayda Baghery Saghchy Khorasani, Amir-Mohammad Yousefi, Davood Bashash
Summary: CAR NK cells have attracted attention as a viable alternative to CAR T cells due to their MHC-independency, shorter life expectancy, potential for off-the-shelf immune product creation, and potent antitumor properties. This article provides an updated review of the differences between CAR T and CAR NK cells, current enhancements in CAR NK design, sources for collecting NK cells, and strategies for transducing CARs to NK cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Editorial Material
Oncology
Amanda M. DiNofia, Stephan A. Grupp
Summary: This study reports the use of allogeneic anti-CD19 CAR T cells in 21 pediatric and adult patients with acute lymphoblastic leukemia. The results provide some insights into the potential of allogeneic CAR T cell therapy as a replacement for autologous CAR T cell therapy, although more data are needed for further comparisons.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Review
Oncology
Hidefumi Hiramatsu
Summary: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and though the long-term survival rate is high at 90%, about 20% of patients experience relapse and need second-line treatment. The introduction of immunotherapy, including CAR-T cell therapy, has revolutionized the treatment of relapsed and refractory ALL. However, CAR-T cell therapy can cause specific adverse events, and the biggest challenge remains preventing relapse. Overall, the success of CD19 CAR-T cell therapy against B cell malignancies has led to further research into its potential for other hematologic malignancies.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Martin G. Klatt, Tao Dao, Zhiyuan Yang, Jianying Liu, Sung Soo Mun, Megan M. Dacek, Hanzhi Luo, Thomas J. Gardner, Christopher Bourne, Leila Peraro, Zita E. H. Aretz, Tanya Korontsvit, Michael Lau, Michael G. Kharas, Cheng Liu, David A. Scheinberg
Summary: Mass spectrometry identified a non-immunogenic HLA ligand as a target for CAR T-cell therapy, which showed broad effectiveness against multiple cancer types, particularly hematologic cancers, and had no toxic effects on healthy cells.
Review
Oncology
Yuqing Wang, Ruihao Huang, Zheng Wang, Jingkang Xiong, Xiaoqi Wang, Xi Zhang
Summary: Since the implementation of allo-HSCT, many patients with hematologic malignancies have achieved a favorable overall survival rate. However, GVHD and complications of immunosuppressive drugs remain major causes of non-relapse mortality and poor quality of life. Moreover, GVHD and toxicity still occur with DLIs and CAR T-cell therapy. Universal immune cell therapy, with its immune tolerance characteristics and anti-tumor ability, has the potential to reduce GVHD and tumor burden. However, its widespread application is hindered by expansion and persistence efficacy issues. Various strategies, such as universal cell lines, signaling regulation, and CAR technology, have been explored to address this challenge. This review summarizes current advances and future perspectives in universal immune cell therapy for hematologic malignancies.
CANCER BIOLOGY & MEDICINE
(2023)
Article
Multidisciplinary Sciences
Yongxian Hu, Jingjing Li, Fang Ni, Zhongli Yang, Xiaohua Gui, Zhiwei Bao, Houli Zhao, Guoqing Wei, Yiyun Wang, Mingming Zhang, Ruimin Hong, Linqin Wang, Wenjun Wu, Mohamad Mohty, Arnon Nagler, Alex H. Chang, Marcel R. M. van den Brink, Ming D. Li, He Huang
Summary: This study compares the gut microbiome diversity and composition during different phases of CAR-T therapy and finds that it is associated with patient response to therapy and occurrence of immune-related adverse effects.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Sarah J. Nagle, Catherine Murphree, Philipp W. Raess, Levanto Schachter, Andy Chen, Brandon Hayes-Lattin, Eneida Nemecek, Richard T. Maziarz
Summary: CAR T-cell therapy is effective in treating patients with R/R DLBCL, but it is associated with significant prolonged hematologic toxicity (PHT) that can affect patients' survival rates. Risk factors associated with PHT include CRS, the use of tocilizumab or steroids, peak levels of ferritin and C-reactive protein. More research is needed to further investigate PHT and establish management standards.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Biology
Zhaoqi Chen, Yan Liu, Nianci Chen, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Yingxi Xu, Ying Wang, Min Wang, Jianxiang Wang
Summary: CD19 chimeric antigen receptor (CAR) T cells have shown success in acute lymphoblastic leukemia but have limited efficacy in other types of leukemia and lymphoma. This study constructed bispecific CAR-T cells targeting both CD19 and CD20 antigens, which demonstrated superior efficacy in eliminating lymphoma cells in vitro and in a mouse model. The loop2019 CAR structure showed the highest efficiency and potential for clinical treatment.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Oncology
Karen Kai-Lin Fang, Jongbok Lee, Ismat Khatri, Yoosu Na, Li Zhang
Summary: The use of allogeneic CAR4-DNTs as adoptive cell therapy for T-cell malignancies is effective. CAR4-DNTs can effectively target T-ALL and PTCL and have superior cytotoxicity compared to empty-vector transduced DNTs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Wingchi K. Leung, Adanma Ayanambakkam, Helen E. Heslop, LaQuisa C. Hill
Summary: The adoptive transfer of CD19-specific CAR-T cells has significantly improved the treatment outcomes for relapsed/refractory CD19 B-cell malignancies. However, the loss of CD19 antigen limits the applicability of CAR-T cells, leading to treatment failure. This review focuses on exploring alternative targets beyond CD19 for CAR-T cell therapy.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Oncology
Alexandra Pender, Emma Titmuss, Erin D. Pleasance, Kevin Y. Fan, Hillary Pearson, Scott D. Brown, Cameron J. Grisdale, James T. Topham, Yaoqing Shen, Melika Bonakdar, Gregory A. Taylor, Laura M. Williamson, Karen L. Mungall, Eric Chuah, Andrew J. Mungall, Richard A. Moore, Jean-Michel Lavoie, Stephen Yip, Howard Lim, Daniel J. Renouf, Sophie Sun, Robert A. Holt, Steven J. M. Jones, Marco A. Marra, Janessa Laskin
Summary: The study investigated the use of WGTA to analyze fresh tumor biopsies from 98 patients with metastatic tumors, revealing that tumor mutation burden, CD8(+) T-cell, and M1-M2 macrophage ratios were significant predictors of treatment response. Combining multiple biomarkers based on WGTA allows for better identification of responders to immune checkpoint inhibitors in a heterogeneous population of advanced and previously treated cancers.
CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Gisell Castillo, Manoj Lalu, Sarah Asad, Madison Foster, Natasha Kekre, Dean Fergusson, Terry Hawrysh, Harold Atkins, Kednapa Thavorn, Joshua Montroy, Stuart Schwartz, Robert Holt, Raewyn Broady, Justin Presseau
Summary: By interviewing hematologists in Canada, it was found that they faced challenges such as lack of resources, high workload, and unclear roles when screening and recruiting patients for early phase immunotherapy trials. However, most physicians expressed intentions and willingness to screen for the trial, while also recognizing the challenges and attempting to find solutions.
Article
Medicine, General & Internal
Gisell Castillo, Manoj M. Lalu, Sarah Asad, Madison Foster, Natasha Kekre, Dean A. Fergusson, Terry Hawrysh, Harold Atkins, Kednapa Thavorn, Joshua Montroy, Stuart Schwartz, Robert A. Holt, Raewyn Broady, Justin Presseau
Summary: Using the Theoretical Domains Framework (TDF), this study identified various factors that influence patient participation in early phase CAR-T cell therapy trials, including patient interests in treatment safety, efficacy, trial logistics, altruism, personal health benefits, medical advice from healthcare providers, and access to financial and social supports. These findings can help optimize recruitment processes and enhance patient engagement in clinical trials.
Editorial Material
Oncology
Rachel Wong, Andrew Nguyen, Xuehai Wang, Lauren Chong, Kateryna Tyshchenko, Scott D. Brown, Rob A. Holt, Christian Steidl, Andrew P. Weng
Article
Multidisciplinary Sciences
Marie S. Rye, Kerryn L. Garrett, Robert A. Holt, Cameron F. Platell, Melanie J. McCoy
Summary: Infiltration of certain bacterial species in the mucosa may contribute to the development of colorectal cancer (CRC). This study aimed to determine the optimal site for bacterial detection in CRC tumors. The presence of Fusobacterium nucleatum and Bacteroides fragilis was detected in tumors from 43% and 24% of patients, respectively. The optimal detection site was found to be the tumor luminal surface. F. nucleatum detection was associated with more advanced disease. The study suggests a role for F. nucleatum in CRC development and highlights the significance of tumor luminal surface for bacterial detection.
Article
Microbiology
Cody A. Despins, Scott D. Brown, Avery Robinson, Andrew J. Mungall, Emma Allen-Vercoe, Robert A. Holt
Summary: The study found that F. nucleatum-induced host cell transcriptional modulation involves strong upregulation of genes related to immune migration and inflammatory processes, in addition to identifying genes strongly upregulated in a cell line-specific manner. Furthermore, extensive host cell epigenomic changes specific to host cell type were observed upon F. nucleatum exposure.
Article
Oncology
Laura M. Williamson, Craig M. Rive, Daniela Di Francesco, Emma Titmuss, Hye-Jung E. Chun, Scott D. Brown, Katy Milne, Erin Pleasance, Anna F. Lee, Stephen Yip, Daniel G. Rosenbaum, Martin Hasselblatt, Pascal D. Johann, Marcel Kool, Melissa Harvey, David Dix, Daniel J. Renouf, Robert A. Holt, Brad H. Nelson, Martin Hirst, Steven J. M. Jones, Janessa Laskin, Shahrad R. Rassekh, Rebecca J. Deyell, Marco A. Marra
Summary: Poorly differentiated chordoma (PDC) primarily affects children with a poor prognosis and limited treatment options. Molecular analysis revealed the presence of tumor-associated immune cells and the expression of immune checkpoint proteins, providing a rationale for immune checkpoint inhibitor therapy. Targeting the brachyury tumor antigen by tumor-associated T cells may underlie the clinical response to immune checkpoint inhibitors.
NPJ PRECISION ONCOLOGY
(2021)
Article
Oncology
Ping Xiang, Xining Yang, Leo Escano, Ishpreet Dhillon, Edith Schneider, Jack Clemans-Gibbon, Wei Wei, Jasper Wong, Simon Xufeng Wang, Derek Tam, Yu Deng, Eric Yung, Gregg B. Morin, Pamela A. Hoodless, Martin Hirst, Aly Karsan, Florian Kuchenbauer, R. Keith Humphries, Arefeh Rouhi
Summary: In this study, we created a knock-in GFP reporter system at the endogenous MEIS1 locus in a human AML cell line to investigate the transcriptional regulatory mechanisms of MEIS1. We identified a critical enhancer region of the MEIS1 locus and found FLI1, an ETS transcription factor, to be an important regulator of MEIS1 transcription. Furthermore, we demonstrated direct binding of FLI1 to the MEIS1 locus in human AML cell lines and observed enrichment of histone acetylation in MEIS1-high healthy and leukemic cells. Additionally, high FLI1 transcript levels were associated with worse overall survival in AML patients.
Editorial Material
Microbiology
Robert A. Holt
Summary: There is growing recognition of the various connections between host-microbe interactions and the onset and progression of cancer. Vaccines targeting oncomicrobes like F. nucleatum, which promote tumorigenesis, may offer novel and successful interventions against colorectal cancer and other diseases.
CELL HOST & MICROBE
(2023)
Article
Biochemical Research Methods
Scott D. Brown, Lisa Dreolini, Jessica F. Wilson, Miruna Balasundaram, Robert A. Holt
Summary: This study presents a cost-effective and accurate plasmid sequencing method using the MinION device from Oxford Nanopore Technologies as an alternative to capillary-based sequencing. The procedure allows for the identification of plasmid identity and mutations, achieving high accuracy in consensus sequence generation. This pipeline offers significant cost savings compared to outsourcing clinical-grade sequencing, providing accessible high-quality plasmid sequence verification.
BMC BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Patrick Coulombe, Grace Cole, Amanda Fentiman, Jeremy D. K. Parker, Eric Yung, Misha Bilenky, Lemlem Degefie, Patrick Lac, Maggie Y. M. Ling, Derek Tam, R. Keith Humphries, Aly Karsan
Summary: The authors identify Meis1 as an early regulator in the specification of hemogenic cells from arterial endothelium. Meis1 is crucial for the formation of functional Runx1-expressing hemogenic endothelial cells, which are necessary for the emergence of hematopoietic stem and progenitor cells.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Nicola Principe, Joel Kidman, Siting Goh, Caitlin M. Tilsed, Scott A. Fisher, Vanessa S. Fear, Catherine A. Forbes, Rachael M. Zemek, Abha Chopra, Mark Watson, Ian M. Dick, Louis Boon, Robert A. Holt, Richard A. Lake, Anna K. Nowak, Willem Joost Lesterhuis, Alison M. McDonnell, Jonathan Chee
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Oncology
Erin Pleasance, Emma Titmuss, Laura Williamson, Harwood Kwan, Luka Culibrk, Eric Y. Zhao, Katherine Dixon, Kevin Fan, Reanne Bowlby, Martin R. Jones, Yaoqing Shen, Jasleen K. Grewal, Jahanshah Ashkani, Kathleen Wee, Cameron J. Grisdale, My Linh Thibodeau, Zoltan Bozoky, Hillary Pearson, Elisa Majounie, Tariq Vira, Reva Shenwai, Karen L. Mungall, Eric Chuah, Anna Davies, Mya Warren, Caralyn Reisle, Melika Bonakdar, Gregory A. Taylor, Veronika Csizmok, Simon K. Chan, Zusheng Zong, Steve Bilobram, Amir Muhammadzadeh, Darryl D'Souza, Richard D. Corbett, Daniel MacMillan, Marcus Carreira, Caleb Choo, Dustin Bleile, Sara Sadeghi, Wei Zhang, Tina Wong, Dean Cheng, Scott D. Brown, Robert A. Holt, Richard A. Moore, Andrew J. Mungall, Yongjun Zhao, Jessica Nelson, Alexandra Fok, Yussanne Ma, Michael K. C. Lee, Jean-Michel Lavoie, Shehara Mendis, Joanna M. Karasinska, Balvir Deol, Ana Fisic, David F. Schaeffer, Stephen Yip, Kasmintan Schrader, Dean A. Regier, Deirdre Weymann, Stephen Chia, Karen Gelmon, Anna Tinker, Sophie Sun, Howard Lim, Daniel J. Renouf, Janessa Laskin, Steven J. M. Jones, Marco A. Marra