Article
Oncology
Holly Pariury, Laurel Truscott, Emmanuel Katsanis
Summary: Recent advancements in the treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL), such as immunotherapies and haploidentical hematopoietic cell transplantation, have provided more options for relapsed patients. These therapies have shown significant efficacy in achieving remission and reducing toxicity, resulting in prolonged survival for patients with B-ALL.
Article
Oncology
Marie-Emilie Dourthe, Florence Rabian, Karima Yakouben, Florian Chevillon, Aurelie Cabannes-Hamy, Francoise Mechinaud, Audrey Grain, Delphine Chaillou, Ilhem Rahal, Sophie Caillat-Zucman, Emmanuelle Lesprit, Jerome Naudin, Julie Roupret-Serzec, Nathalie Parquet, Anne Brignier, Valerie Guerin-El Khourouj, Elodie Lainey, Aurelie Caye-Eude, Helene Cave, Emmanuelle Clappier, Stephanie Mathis, Elie Azoulay, Jean Hugues Dallel, Nathalie Dhedin, Isabelle Madelaine, Jerome Larghero, Nicolas Boissel, Andre Baruchel
Summary: Tisagenlecleucel therapy has shown promising efficacy in relapsed/refractory BCP-ALL patients, with a high complete remission rate at D28. However, factors such as prior therapy and disease burden can impact the risk of relapse and overall survival. Detectable MRD at D28 and loss of BCA may define patients at high risk of relapse, requiring additional interventions.
Article
Oncology
Sisi Wang, Lijun Peng, Wenqian Xu, Yuebo Zhou, Ziyan Zhu, Yushan Kong, Stewart Leung, Jin Wang, Xiaoqiang Yan, Jian-Qing Mi
Summary: The newly designed antibodies A-319 and A-2019 showed potent antitumor effects in vitro, ex vivo, and in vivo experiments. A-319 and A-2019 are CD3/CD19 and CD3/CD19/CD20 bispecific and trispecific antibodies, respectively, capable of recruiting T cells, enhancing T-cell function, mediating B-cell depletion, and inhibiting tumor growth.
FRONTIERS OF MEDICINE
(2022)
Article
Oncology
Na Zhang, Jingbo Shao, Hong Li, Jiashi Zhu, Min Xia, Kai Chen, Hui Jiang
Summary: This study evaluated the efficacy and neurotoxicity of chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory acute lymphoblastic leukemia patients. The results showed good efficacy of CAR-T therapy in patients with central nervous system leukemia or neurological comorbidities, but some patients experienced severe neurotoxicity. The expansion of CAR-T cells in cerebrospinal fluid also demonstrated the effectiveness of CAR-T therapy.
JOURNAL OF IMMUNOTHERAPY
(2022)
Review
Pharmacology & Pharmacy
Andreas Viardot, Elisa Sala
Summary: The anti-CD19 immunotherapy has shown significant potential for treating B-precursor acute lymphoblastic leukemia (B-ALL), with major advances in CD19 monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engaging antibodies and adoptive cellular therapies such as CAR-Ts. Experimental anti-CD19 antibodies or CAR-Ts may overcome limitations of toxicity, rapid clearance, or resistance, suggesting promising results for novel cellular constructs.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Review
Hematology
Theodore W. Laetsch, Gregory A. Yanik, Michael W. Boyer, Susan R. Rheingold
Summary: CAR-T cell therapy has shown durable responses and manageable safety profile in pediatric and young adult patients with relapsed or refractory B-ALL, including patient selection, preparation, cell infusion, and monitoring and management of short- and long-term safety events.
Article
Immunology
Yao Sun, Yongfeng Su, Yizhi Wang, Na Liu, Yuhang Li, Jianlin Chen, Zhuoqing Qiao, Jingwen Niu, Jiangwei Hu, Bin Zhang, Hongmei Ning, Liangding Hu
Summary: The study presented a case of a patient with B-ALL who experienced extramedullary relapse after allogeneic stem cell transplantation and underwent multiple CAR-T cell therapies, including different variants of CD19 CAR-T cells. The patient achieved therapeutic responses after some of the treatments, demonstrating the potential efficacy of CAR-T cell therapy in relapsed B-ALL patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Yuekun Qi, Mingfeng Zhao, Yongxian Hu, Ying Wang, Ping Li, Jiang Cao, Ming Shi, Jiaqi Tan, Meng Zhang, Xia Xiao, Jieyun Xia, Sha Ma, Jianlin Qiao, Zhiling Yan, Hujun Li, Bin Pan, Wei Sang, Depeng Li, Zhenyu Li, Jianfeng Zhou, He Huang, Aibin Liang, Junnian Zheng, Kailin Xu
Summary: This study evaluated the efficacy and safety of CD19-specific CAR T-cell therapy for patients with B-ALL and CNSL. The results showed high response rates in both BM and CNS diseases, with longer remission duration in CNSL, suggesting it as a potential treatment option for previously excluded patients with CNSL.
Article
Oncology
Xian Zhang, Junfang Yang, Jingjing Li, Wenqian Li, Dan Song, Xin-An Lu, Fei Wu, Jianqiang Li, Dandan Chen, Xiangqun Li, Zhongwei Xu, Shuqiang Liu, Ziyu Li, Kui Ying, Peihua Lu
Summary: TP53 mutation and bone marrow blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts < 5% can benefit from consolidative allo-HSCT post-CAR-T therapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Immunology
Ying Pan, Huiping Wang, Furun An, Fan Wu, Qianshan Tao, Yingwei Li, Yanjie Ruan, Zhimin Zhai
Summary: This study found that higher levels of circulating Tregs, especially one week after CD19 CAR-T cell infusion, served as a poor predictor for CD19 CAR-T therapy in R/R B-ALL patients, indicating a significant association with treatment efficacy and prognosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Antonella Mancusi, Francesco Zorutti, Loredana Ruggeri, Samanta Bonato, Sara Tricarico, Tiziana Zei, Roberta Iacucci Ostini, Valerio Viglione, Rebecca Sembenico, Sofia Sciabolacci, Valeria Cardinali, Massimo Fabrizio Martelli, Cristina Mecucci, Alessandra Carotti, Maria Paola Martelli, Andrea Velardi, Antonio Pierini
Summary: This study demonstrates the feasibility of using blinatumomab and DLI to treat relapses after Treg/Tcon haploidentical HSCT, and suggests that their preemptive use could improve efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Audrey Grain, Jocelyn Ollier, Thierry Guillaume, Patrice Chevallier, Baptiste Le Calvez, Marion Eveillard, Beatrice Clemenceau
Summary: This study explores the immunophenotyping and lysis sensitivity of CD19(+) relapses after anti-CD19 CAR-T cells and proposes different therapeutic options. The results show that CD19(+) relapses remain sensitive to cell lysis mediated by T-cell effectors. A broad immunophenotype analysis may provide new therapies for controlling high-risk ALL after immunotherapy.
Article
Hematology
Cory Seth Bridges, Taylor J. Chen, Monica Puppi, Karen R. Rabin, H. Daniel Lacorazza
Summary: Novel drugs, such as OTSSP167, have been shown to have antileukemic capacity in children with high-risk T-cell acute lymphoblastic leukemia (T-ALL). OTSSP167 inhibits MAP2K7 kinase activity and the downstream substrate, JNK, leading to apoptosis and cell cycle arrest in T-ALL cell lines. It also exhibits synergistic effects when combined with other drugs and shows potential as an adjuvant treatment to enhance response and reduce relapses in pediatric T-ALL.
Article
Oncology
Gabriela M. Maron, Diego R. Hijano, Rebecca Epperly, Yin Su, Li Tang, Randall T. Hayden, Swati Naik, Seth E. Karol, Stephen Gottschalk, Brandon M. Triplett, Aimee C. Talleur
Summary: CD19-specific CAR T cell therapy has revolutionized the treatment of relapsed/refractory B-ALL in pediatric and AYA patients. However, the infectious disease challenges associated with this therapy are not well understood. This study examines the infections that occurred in pediatric and AYA patients after receiving CD19-CAR T cells and identifies risk factors for infection. The results show that infections are common in the first 90 days after CAR T cell therapy, with bacterial infections being more frequent early on and viral infections occurring throughout the post-infusion period. The study highlights the need for further research to improve surveillance, prophylaxis, and treatment strategies for infectious complications.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Omar Perbellini, Chiara Cavallini, Roberto Chignola, Marilisa Galasso, Maria T. Scupoli
Summary: This study reveals a high variability in signaling networks across different T-ALL cell lines and provides insight into the characterization of these differences using phospho-specific flow cytometry.
Article
Surgery
N. Macesic, D. Langsford, K. Nicholls, P. Hughes, D. J. Gottlieb, L. Clancy, E. Blyth, K. Micklethwaite, B. Withers, S. Majumdar, S. Fleming, J. Sasadeusz
AMERICAN JOURNAL OF TRANSPLANTATION
(2015)
Article
Hematology
Kenneth F. Bradstock, Ian Bilmon, John Kwan, Kenneth Micklethwaite, Emily Blyth, Stephanie Deren, Angela Bayley, Val Gebski, David Gottlieb
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2015)
Article
Hematology
Kenneth Bradstock, Ian Bilmon, John Kwan, Emily Blyth, Kenneth Micklethwaite, Gillian Huang, Stephanie Deren, Karen Byth, David Gottlieb
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2015)
Article
Cell & Tissue Engineering
Saumya Ravianayake, Ian Bilmon, David Bishop, Ming-Celine Dubosq, Emily Blyth, Leighton Clancy, David Gottlieb, Kenneth Micklethwaite
Article
Cell & Tissue Engineering
Chun K. K. Ma, Emily Blyth, Leighton Clancy, Renee Simms, Jane Burgess, Rebecca Brown, Shivashni Deo, Kenneth P. Micklethwaite, David J. Gottlieb
Article
Cell & Tissue Engineering
Sylvie Shen, Ning Xu, Guy Klamer, Kap-Hyoun Ko, Melissa Khoo, David Ma, John Moore, Tracey A. O'Brien, Alla Dolnikov
STEM CELLS AND DEVELOPMENT
(2015)
Article
Oncology
Benjamin Y. Kong, Kenneth P. Micklethwaite, Sanjay Swaminathan, Richard F. Kefford, Matteo S. Carlino
Article
Hematology
Chun K. K. Ma, Leighton Clancy, Renee Simms, Jane Burgess, Shivashni Deo, Emily Blyth, Kenneth R. Micklethwaite, David J. Gottlieb
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2018)
Review
Biochemistry & Molecular Biology
Kavitha Gowrishankar, Lucy Birtwistle, Kenneth Micklethwaite
Article
Biotechnology & Applied Microbiology
David C. Bishop, Ning Xu, Benjamin Tse, Tracey A. O'Brien, David J. Gottlieb, Alla Dolnikov, Kenneth P. Micklethwaite
Article
Medicine, General & Internal
David Kliman, Ian Bilmon, John Kwan, Emily Blyth, Ken Micklethwaite, Shyam Panicker, Abir Bhattacharyya, Stephanie Deren, Vicki Antonenas, Gillian Huang, David Gottlieb
INTERNAL MEDICINE JOURNAL
(2018)
Article
Medicine, Research & Experimental
Gaurav Sutrave, Ning Xu, Tiffany C. Y. Tang, Alla Dolnikov, Brian Gloss, David J. Gottlieb, Kenneth P. Micklethwaite, Kavitha Gowrishankar
Summary: CAR T cells targeting CD19 show significant efficacy in treating B cell malignancies, but current manufacturing protocols are complex and costly. This study highlights the potential of utilizing the transposase piggyBat from little brown bats for efficient production of CAR T cells with low variability and similar integration site profiles.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Cell & Tissue Engineering
Guy Klamer, Jessica Sue, Annette Trickett, Kap-Hyoun Ko, Phillip Johnson, Ngaire J. Elwood
Summary: The analysis of the network of public cord blood banks in Australia reveals that stored cord blood units have unique tissue types and HLA alleles associated with specific ethnicities. This suggests that the continuous addition of cord blood units can increase the diversity of HLA and strategic collection sites can facilitate the collection of rare HLA associated with ethnic minority groups. These findings are significant for the field of cell and gene therapy.
Article
Cell & Tissue Engineering
Chun K. K. Ma, Leighton Clancy, Shivashni Deo, Emily Blyth, Kenneth P. Micklethwaite, David J. Gottlieb