Review
Immunology
Jaquelyn T. Zoine, Sarah E. Moore, M. Paulina Velasquez
Summary: This paper discusses preclinical modeling of leukemia ACT and emphasizes the importance of syngeneic mouse models. Syngeneic models can better evaluate the impact of immunosuppressive leukemia microenvironment on treatment outcomes, contributing to the improvement of leukemia therapy strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Fatemeh Rahbarizadeh
Summary: CAR-T therapy has shown remarkable success in treating B-ALL, but faces challenges such as adverse events and immune-related issues. Advances in media design and other factors may lead to more effective therapy in the future.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Patrycja Sliwa-Tytko, Agnieszka Kaczmarska, Monika Lejman, Joanna Zawitkowska
Summary: Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL). However, both chemotherapy and immunotherapy cause side effects, including neurological ones. Neurotoxicity associated with specific chemotherapy drugs and CAR T-cell therapy are major concerns.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Rosa A. van Amerongen, Renate S. Hagedoorn, Dennis F. G. Remst, Danique C. Assendelft, Dirk M. van der Steen, Anne K. Wouters, Marian van de Meent, Michel G. D. Kester, Arnoud H. de Ru, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: In this study, high-avidity WT1-specific T cells were identified from the allogeneic T-cell repertoire of healthy donors. These T cells showed potent and specific anti-WT1 activity against newly identified WT1 peptides derived from primary leukemia and ovarian carcinoma samples. Additionally, T-cell clones with T-cell receptor (TCR) gene transfer showed antitumor reactivity against WT1-expressing solid tumor cell lines, acute myeloid leukemia (AML) blasts, and ovarian carcinoma patient samples. These findings suggest that these TCRs and naturally expressed WT1 peptides have potential for TCR gene transfer strategies in patients with WT1-expressing tumors, including AML and ovarian carcinoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Anca Viorica Ivanov, Mirabela Smaranda Alecsa, Roxana Popescu, Magdalena Iuliana Starcea, Adriana Maria Mocanu, Cristina Rusu, Ingrith Crenguta Miron
Summary: In the past 40 years, the survival rate for pediatric cancer has greatly improved, reaching 75-80%. However, leukemia still remains a major cause of morbidity and mortality in specific patient populations. The future of leukemia treatment lies in molecular therapies, immune therapy, and cellular therapy. Recent advances in the field have led to the development of novel therapies for childhood leukemia, including targeted therapies and immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Silvia Jimenez-Morales, Ivan Sammir Aranda-Uribe, Carlos Jhovani Perez-Amado, Julian Ramirez-Bello, Alfredo Hidalgo-Miranda
Summary: Acute lymphoblastic leukemia (ALL) is a malignancy characterized by high heterogeneity in its biological features and treatment responses. Despite significant improvements in overall survival (OS) with conventional chemotherapy, relapse rates remain high due to mechanisms such as clonal evolution, chemoresistance, and immune evasion by ALL cells. Immunotherapy in combination with traditional treatments has shown promise in improving OS for ALL patients, highlighting the importance of understanding immune evasion mechanisms in developing novel therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Anna Aureli, Beatrice Marziani, Adriano Venditti, Tommaso Sconocchia, Giuseppe Sconocchia
Summary: The emergence of targeted therapies has revolutionized the management of B-lineage acute lymphoblastic leukemia, allowing for optimism in replacing traditional treatments. However, few patients currently benefit from these therapies, necessitating further research to improve outcomes, particularly in patients resistant to current treatments. This review discusses new therapeutic options, including bispecific antibodies, antibody-drug conjugates, and CAR-based therapies.
Review
Immunology
Shanie Saghafian-Hedengren, Eva Sverremark-Ekstrom, Anna Nilsson
Summary: The article summarizes the role of the immune system in recognizing and eliminating malignant cells, and discusses the potential challenges faced by T-cell immunotherapies targeting pediatric cancers in early life stages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Anais Jimenez-Reinoso, Nestor Tirado, Alba Martinez-Moreno, Victor M. Diaz, Marina Garcia-Peydro, Oana Hangiu, Laura Diez-Alonso, Angela Albitre, Petronila Penela, Maria L. Toribio, Pablo Menendez, Luis Alvarez-Vallina, Diego Sanchez Martinez
Summary: CD1a-STAb T cells could be an alternative to CD1a-CAR T cells for coT-ALL patients with aggressive and hyperleukocytic relapses and limited numbers of non-leukemic effector T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Alvaro Haroun-Izquierdo, Marianna Vincenti, Herman Netskar, Hanna van Ooijen, Bin Zhang, Laura Bendzick, Minoru Kanaya, Pouria Momayyezi, Shuo Li, Merete Thune Wiiger, Hanna Julie Hoel, Silje Zandstra Krokeide, Veronika Kremer, Geir Tjonnfjord, Stephanie Berggren, Kristina Wikstroem, Pontus Blomberg, Evren Alici, Martin Felices, Bjoern oenfelt, Petter Hoeglund, Bahram Valamehr, Hans-Gustaf Ljunggren, Andreas Bjoerklund, Quirin Hammer, Lise Kveberg, Frank Cichocki, Jeffrey S. Miller, Karl-Johan Malmberg, Ebba Sohlberg
Summary: This study demonstrates the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population for hematological malignancies. The expanded adaptive NK cells retained high cytotoxicity and efficiently killed leukemia cells from AML patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Chana L. Glasser, Jing Chen
Summary: The treatment for relapsed acute lymphoblastic leukemia (ALL) in children and young adults is constantly evolving. Immunotherapy has revolutionized the field by harnessing the patient's immune system to target and eliminate leukemia cells. Novel immunotherapies, such as blinatumomab, inotuzumab, daratumomab, and chimeric antigen receptor T-cell therapy, show promising potential to enhance outcomes while reducing toxicity.
Article
Chemistry, Medicinal
Leticia Eligio Garcia, Maria Del Pilar Crisostomo Vazquez, Victor Alberto Maravelez Acosta, Mariana Soria Guerrero, Adrian Cortes Campos, Enedina Jimenez Cardoso
Summary: This study aimed to determine the presence of antigenic proteins of T. cruzi shared with acute lymphoblastic leukemia and neuroblastoma cells. The results contribute to a better understanding of the immune interactions between cancer and parasites, and provide insights for the design of cancer therapies.
Article
Immunology
Han-Yu Cao, Hui Chen, Song-Bai Liu, Wen-Jie Gong, Chong-Sheng Qian, Tong-Tong Zhang, Chao-Ling Wan, Si-Man Huang, Nan Xu, Hai-Ping Dai, Sheng-Li Xue
Summary: The treatment of B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement is challenging due to weak permeability of chemotherapeutic agents to the blood-brain barrier (BBB) and potential complications of current anti-CNS leukemia treatments. Immunotherapy, particularly blinatumomab, shows potential in treating CNS leukemia with both cerebral spinal fluid and cerebral parenchymal involvement, but further studies are needed.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Oncology
Sofie Snipstad, Frida Bremnes, Mats Dehli Haugum, Einar Sulheim
Summary: This study characterized six different immunocompetent murine models based on four different cell lines, including metastatic lung cancer, triple-negative breast cancer, pancreatic cancer, and colon cancer. The responsiveness toward anti-PD1 checkpoint inhibitor varied among these models, providing insights into the heterogeneity of immune responses to immunotherapies.
Article
Medicine, Research & Experimental
Ivetta Danylesko, Guy Chowers, Roni Shouval, Michal J. Besser, Elad Jacoby, Avichai Shimoni, Arnon Nagler, Abraham Avigdor
CURRENT RESEARCH IN TRANSLATIONAL MEDICINE
(2020)
Article
Hematology
Daphna Hutt, Bella Bielorai, Bella Baturov, Inna Z'orbinski, Natalia Ilin, Etai Adam, Orit Itzhaki, Michal J. Besser, Amos Toren, Elad Jacoby
TRANSFUSION AND APHERESIS SCIENCE
(2020)
Article
Oncology
Orit Itzhaki, Elad Jacoby, Abraham Nissani, Michal Levi, Arnon Nagler, Adva Kubi, Karin Brezinger, Hadar Brayer, Li-at Zeltzer, Meir Rozenbaum, Helly Vernitsky, Gal Markel, Amos Toren, Abraham Avigdor, Jacob Schachter, Michal J. Besser
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Immunology
Meir Rozenbaum, Amilia Meir, Yarden Aharony, Orit Itzhaki, Jacob Schachter, Ilan Bank, Elad Jacoby, Michal J. Besser
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Biophysics
Ivetta Danylesko, Roni Shouval, Noga Shem-Tov, Ronit Yerushalmi, Elad Jacoby, Michal J. Besser, Avichai Shimoni, Tima Davidson, Katia Beider, Dror Mevorach, Shalev Fried, Arnon Nagler, Abraham Avigdor
Summary: After treatment with anti-CD19 CAR T cells, some patients showed pseudo-progression which could be attributed to immune activation of CAR T cells. Further studies are needed to describe and evaluate the impact of this phenomenon.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Talya Wittmann Dayagi, Gilad Sherman, Bella Bielorai, Etai Adam, Michal J. Besser, Avichai Shimoni, Arnon Nagler, Amos Toren, Elad Jacoby, Abraham Avigdor
Summary: Infections following CAR T-cell therapy primarily consist of bacterial and viral infections, which are associated with neutropenia, fever, and poor response to treatment. Children experience less severe infections compared to adults, with treatment failure being the main significant risk factor identified in multivariate analysis.
LEUKEMIA & LYMPHOMA
(2021)
Article
Biophysics
Yarden Greental Ness, Amir A. Kuperman, Jerry Stein, Joanne Yacobovich, Ehud Even-Or, Irina Zaidman, Aharon Gefen, Neta Nevo, Bernice Oberman, Amos Toren, Polina Stepensky, Bella Bielorai, Elad Jacoby
Summary: The results of a national retrospective study in Israel involving 45 children with HLH undergoing HSCT showed a 5-year overall survival rate of 86% and event-free survival rate of 82%. Patients receiving RIC had lower 5-year EFS compared to MAC patients, and alternative donor transplants had higher transplant-related mortality rates. Therefore, a myeloablative conditioning regimen may benefit both HLA-matched and alternative donor transplant procedures.
BONE MARROW TRANSPLANTATION
(2021)
Article
Biophysics
Michael H. Albert, Mehtap Sirin, Manfred Hoenig, Fabian Hauck, Catharina Schuetz, Rajat Bhattacharyya, Polina Stepensky, Elad Jacoby, Tayfun Gungor, Rita Beier, Ansgar Schulz
Summary: The study found that a post-transplantation cyclophosphamide-based HLA-haploidentical salvage HSCT after irradiation-free conditioning resulted in excellent engraftment and overall survival in children with non-malignant diseases.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Abraham Nissani, Shaked Lev-Ari, Tomer Meirson, Elad Jacoby, Nethanel Asher, Guy Ben-Betzalel, Orit Itzhaki, Ronnie Shapira-Frommer, Jacob Schachter, Gal Markel, Michal J. Besser
Summary: Different non-myeloablative (NMA) regimens using cyclophosphamide or total body irradiation (TBI) combined with fludarabine have varying impacts on bone marrow suppression and recovery, with the 60Cy/125Flu preconditioning appearing to achieve maximum effect with minimum toxicity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Carlos A. Garcia-Prieto, Lorea Villanueva, Alberto Bueno-Costa, Veronica Davalos, Europa Azucena Gonzalez-Navarro, Manel Juan, Alvaro Urbano-Ispizua, Julio Delgado, Valentin Ortiz-Maldonado, Francesca Del Bufalo, Franco Locatelli, Concetta Quintarelli, Matilde Sinibaldi, Marta Soler, Manuel Castro de Moura, Gerardo Ferrer, Rocio G. Urdinguio, Agustin F. Fernandez, Mario F. Fraga, Diana Bar, Amilia Meir, Orit Itzhaki, Michal J. Besser, Abraham Avigdor, Elad Jacoby, Manel Esteller
Summary: This study revealed that the DNA methylation landscape of patient CART19 cells influences the efficacy of cellular immunotherapy treatment in patients with B-cell malignancies. The establishment of an epigenetic signature, termed EPICART, associated with complete response, was found to be predictive of patient clinical outcomes.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Cell & Tissue Engineering
Elad Jacoby, Moriya Ben Yakir-Blumkin, Shiri Blumenfeld-Kan, Yehuda Brody, Amilia Meir, Naomi Melamed-Book, Tina Napso, Gat Pozner, Esraa Saadi, Ayelet Shabtay-Orbach, Natalie Yivgi-Ohana, Noa Sher, Amos Toren
Summary: The study introduces a novel approach called Mitochondrial Augmentation Therapy (MAT) that can ex vivo augment hematopoietic stem and progenitor cells (HSPCs) with normal exogenous mitochondria, improving their mitochondrial content and oxygen consumption, and showing potential disease-modifying therapy effects in animal models.
NPJ REGENERATIVE MEDICINE
(2021)
Article
Hematology
Elad Jacoby, Bella Bielorai, Daphna Hutt, Orit Itzhaki, Etai Adam, Diana Bar, Michal J. Besser, Amos Toren
Summary: This study reported the long-term outcome of 37 children and young adults treated with autologous CD19 CAR-T cells, with a complete remission rate of 86% and 41% three-year EFS. Prelymphodepletion disease burden and molecular MRD negativity following CAR-T cells are predictors of long-term outcome.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Elad Jacoby, Sara Ghorashian, Britta Vormoor, Barbara De Moerloose, Nicole Bodmer, Olga Molostova, Asaf D. Yanir, Jochen Buechner, Ronit Elhasid, Bella Bielorai, Srdan Rogosic, Marie-Emilie Dourthe, Michael Maschan, Claudia Rossig, Amos Toren, Arend von Stackelberg, Franco Locatelli, Peter Bader, Martin Zimmermann, Jean Pierre Bourquin, Andre Baruchel
Summary: CAR T-cell therapy shows effectiveness in treating relapsed BCP-ALL patients with CNS involvement, but the risk of neurotoxicity and CNS relapse remains.
Article
Hematology
Sara Ghorashian, Elad Jacoby, Barbara De Moerloose, Susana Rives, Denise Bonney, Geoff Shenton, Peter Bader, Nicole Bodmer, Agueda Molinos Quintana, Blanca Herrero, Mattia Algeri, Franco Locatelli, Kim Vettenranta, Berta Gonzalez, Andishe Attarbaschi, Stephen Harris, Jean Pierre Bourquin, Andre Baruchel
Summary: This study analyzed the feasibility, efficacy, and safety of tisagenlecleucel treatment in young children and infants with acute lymphoblastic leukemia. The results suggest that tisagenlecleucel has antitumor activity and an acceptable safety profile for this age group.
LANCET HAEMATOLOGY
(2022)
Article
Hematology
Meirav Kedmi, Roni Shouval, Shalev Fried, David Bomze, Joshua Fein, Zachary Cohen, Ivetta Danilesko, Noga Shem-Tov, Ronit Yerushalmi, Elad Jacoby, Michal Besser, Avichai Shimoni, Arnon Nagler, Abraham Avigdor
Summary: Anti CD19 CAR T-cell therapy has shown good efficacy in relapsed and refractory aggressive B-cell lymphoma. Locally produced autologous CD19-directed CAR T-cell product with a short production time and good progression-free and overall survival is a feasible therapeutic option.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)