Article
Immunology
Rui Zheng, Yuankun Chen, Yiting Zhang, Sixin Liang, Xiaojuan Zhao, Yiyi Wang, Pengju Wang, Ruotong Meng, Angang Yang, Bo Yan
Summary: Our study explores the effect of low-affinity CARs using humanized scFvs on the function of CAR-T cells. We find that moderately reducing the affinity of CARs can maintain anti-tumor efficacy and improve the safety of CAR therapy both in vitro and in vivo. In addition, T cells expressing the VL domain only antibody show long-lasting tumor elimination capability and lower cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Peng Zhang, Yang Zhang, Nan Ji
Summary: Glioblastoma (GBM) is a deadly brain cancer with limited efficacy of standard treatments, necessitating the development of new therapies. Chimeric antigen receptor T (CAR-T) cell immunotherapy has shown success in hematological malignancies, but has not yet yielded promising results in GBM. CAR-T cell therapy for GBM faces challenges including tumor heterogeneity, immunosuppressive microenvironment, and cell persistence.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Christopher A. Pennell, Heather Campbell, Meghan D. Storlie, Sara Bolivar-Wagers, Mark J. Osborn, Yosef Refaeli, Michael Jensen, Sophie Viaud, Travis S. Young, Bruce R. Blazar
Summary: Current FDA-approved CAR-T cell therapies for B-cell malignancies are effective but can increase morbidity and mortality. This study compared the performances of regulatable and constitutively active CAR-T cells, and found that regulatable CAR-T cells have the potential for improved efficacy and reduced toxicity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Sophia Stock, Anna-Kristina Kluever, Stefan Endres, Sebastian Kobold
Summary: Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in treating specific hematological malignancies. However, many patients do not respond or relapse after treatment. Strategies such as combining CAR T cells with other treatments and using clinically approved compounds have been investigated to improve this therapy.
Review
Immunology
Bu-Fan Xiao, Jing-Tao Zhang, Yu-Ge Zhu, Xin-Run Cui, Zhe-Ming Lu, Ben-Tong Yu, Nan Wu
Summary: CAR-T cell therapy has shown significant clinical responses in hematological malignancies and is now being evaluated for treating solid tumors. Challenges in using CAR-T cells for lung cancer treatment include on-target, off-tumor toxicity, scarcity of tumor-specific antigen targets, T cell exhaustion, and low immune cell infiltration levels. Advances in tumor immunology and cell product manufacturing are driving the clinical translation of CAR-T cell therapy for lung cancer.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Sophia Stock, Anna-Kristina Kluever, Luisa Fertig, Vivien D. Menkhoff, Marion Subklewe, Stefan Endres, Sebastian Kobold
Summary: The clinical application of CAR T-cell therapy has revolutionized the treatment options for certain terminally ill patients with blood-borne cancers. However, the therapy can lead to severe toxicities, and efforts are being made to better control CAR T-cell activity and manage its associated side effects through various strategies and mechanisms.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Clinical Neurology
Lisa Feldman, Christine Brown, Behnam Badie
Summary: CAR T-cell therapy, utilizing genetically engineered cells from patients to target tumor cells, has emerged as a promising strategy for treating GBM. Ongoing clinical trials are exploring the potential of this approach to combat the challenges associated with GBM treatment.
Review
Oncology
Mahasha P. J. Perera, Patrick B. Thomas, Gail P. Risbridger, Renea Taylor, Arun Azad, Michael S. Hofman, Elizabeth D. Williams, Ian Vela
Summary: This review discusses the role of CAR-T cell therapy in men with metastatic castrate-resistant prostate cancer. Prostate cancer is the most commonly diagnosed solid-organ cancer in males worldwide. Men with metastatic castrate-resistant prostate cancer have limited treatment options, and current therapies are not curative. CAR-T cell therapy has shown success in the treatment of treatment-resistant hematological malignancies, and there are ongoing studies investigating its utility in solid tumors. However, preliminary clinical trials in men with prostate cancer have had limited efficacy, indicating the need for further research to enhance understanding and translation of this therapy.
Review
Medicine, Research & Experimental
Yuxi Luo, Guiqin Song, Shichu Liang, Feifei Li, Kang Liu
Summary: CAR-modified T-cells, a novel cancer immunotherapy, target specific surface antigens on tumor cells through genetic engineering. While showing notable efficacy in hematological tumor treatment, challenges exist in treating solid tumors, along with specific side effects associated with CAR T-cell therapy.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Review
Biochemical Research Methods
Cuilin Zhang, Qiuyu Zhuang, Jingfeng Liu, Xiaolong Liu
Summary: Synthetic biology is an interdisciplinary research area that uses engineering principles to design and construct biological systems for practical applications. Chimeric antigen receptor (CAR) T cells, as one of the most successful clinical applications of synthetic biology, have shown tremendous success in treating blood malignancies. However, there are still limitations to CAR T cell therapy, hence the need for innovative CAR design becomes urgent.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Oncology
Nattaporn Phanthaphol, Chalermchai Somboonpatarakun, Kwanpirom Suwanchiwasiri, Thaweesak Chieochansin, Jatuporn Sujjitjoon, Sopit Wongkham, John Maher, Mutita Junking, Pa-thai Yenchitsomanus
Summary: CAR T cell therapy has shown efficacy in hematologic malignancies, but further investigation is needed for its application in solid tumors. The selection of target antigens highly expressed in cancer cells but not normal cells is crucial for successful immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Clinical Neurology
Renata Ursu, Didier Maillet, Catherine Belin, Christine Moroni, Stefania Cuzzubbo, Victoria Vernier, Lila Sirven-Villaros, Christophe Carreau, Roberta Di Blasi, Catherine Thieblemont, Antoine F. Carpentier
Summary: No significant neurocognitive or neurologic disorders were observed in patients 2 years after treatment with anti-CD19 CAR T cells. Anxiety scores were reduced, but 32% of patients still reported cognitive complaints.
Review
Biochemistry & Molecular Biology
Rui Mao, Mohamed S. Hussein, Yukai He
Summary: This article reviews the factors that affect the activation, effector function, in vivo persistence, and antitumor effects of chimeric antigen receptor T cells (CAR-T). These factors include T cell subsets, CAR design, expression promoters and delivery vectors, and CAR-T production process. The comparison between CAR signaling and TCR activation is also discussed. The article provides insights into CAR design for solid tumors, focusing on strategies to improve CAR-T tumor infiltration and survival in the hostile tumor microenvironment.
EXPERT REVIEWS IN MOLECULAR MEDICINE
(2022)
Article
Immunology
Bilge Debelec-Butuner, Oliver Quitt, Sophia Schreiber, Frank Momburg, Karin Wisskirchen, Ulrike Protzer
Summary: Despite the availability of a prophylactic vaccine, many people still die from hepatitis B virus (HBV)-related liver disease. Current antiviral therapies are not curative, so new strategies are urgently needed. This study explores the use of bi- and trispecific T-cell engager antibodies as an alternative treatment for HBV.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jingting Min, Chirong Long, Lu Zhang, Jiakang Duan, Honglian Fan, Fei Chu, Zhenghong Li
Summary: Non-small cell lung cancer (NSCLC) is a prevalent and fatal malignancy, and CAR-T cell therapy targeting c-Met shows potential as a therapeutic strategy. In vitro and in vivo experiments demonstrated that c-Met CAR-T cells exhibit enhanced cytotoxicity against NSCLC cells.
Meeting Abstract
Hematology
David A. Sallman, Hany Elmariah, Kendra Sweet, Asmita Mishra, Cheryl A. Cox, Marion Chakaith, Roshanak Semnani, Sheeba Shehzad, Asha Anderson, Helen Sabzevari, Amy Lankford, Onyee Chan, Luis SanchezMolina, Chen Wang, Eric Padron, Andrew Kuykendall, Rami S. Komrokji, Jeffrey E. Lancet, Marco L. Davila, Nelli Bejanyan
Meeting Abstract
Hematology
Payal Goala, Hiroshi Kotani, Zhang Yongliang, Kayla M. Reid, Justin C. Boucher, Constanza Savid-Frontera, Sae Bom Lee, Nolan Beatty, Michael D. Jain, Marco L. Davila
Meeting Abstract
Hematology
Kai Rejeski, Ariel Perez Perez, Gloria Iacoboni, Veit L. Buecklein, Viktoria Blumenberg, Simon Voelkl, Olaf Penack, Omar Albanyan, Simon Kg Forsberg, Agnese Petrera, Niklas Mueller, Kayla M. Reid, Rawan Faramand, Marco L. Davila, Michael von Bergwelt, Frederick L. Locke, Wolfgang Bethge, Lars Bullinger, Andreas Mackensen, Pere Barba, Michael D. Jain, Marion Subklewe
Meeting Abstract
Hematology
Justin C. Boucher, Bishwas Shrestha, Paresh Vishwasrao, Mark B. Leick, Nhan Tu, Tayyebb Ghafoor, Kayla M. Reid, Kristen Spitler, Bin Yu, Marcela Maus, Marco L. Davila
Meeting Abstract
Hematology
Hany Elmariah, Jongphil Kim, Kayla M. Reid, Christopher Cubitt, Andrew Kuykendall, Jeffrey E. Lancet, Rami S. Komrokji, David A. Sallman, Onyee Chan, Kendra Sweet, Albert J. Ribickas, Rawan Faramand, Asmita Mishra, Farhad Khimani, Lia Perez, Debra Kessler, Stephanie Dormesy, Joseph Pidala, Claudio Anasetti, Ephraim J. Fuchs, Michael D. Jain, Frederick L. Locke, Marco L. Davila, Nelli Bejanyan, Amy E. DeZern
Article
Oncology
Justin C. Boucher, Bin Yu, Gongbo Li, Bishwas Shrestha, David Sallman, Ana Marie Landin, Cheryl Cox, Kumar Karyampudi, Claudio Anasetti, Marco L. Davila, Nelli Bejanyan
Summary: Higher gamma delta T cell counts in patients with malignancies are associated with better survival. Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous gamma delta T cells using zoledronic acid (zol) and interleukin-2 (IL-2). In this study, we demonstrated that a combination of zol and IL-2, along with a novel genetically engineered aAPC, effectively expanded allogeneic donor-derived gamma delta T cells in large quantities for potential clinical use.
JOURNAL OF IMMUNOTHERAPY
(2023)
Editorial Material
Oncology
Marco L. Davila, Renier J. Brentjens
Summary: Recent progress in CAR T cell biology has improved our understanding of the mechanisms behind durable remissions in some patients. Additionally, promising clinical trial outcomes are being observed in the treatment of solid tumor malignancies using CAR T cells targeting B cell tumor antigens.
Article
Cell Biology
Johannes F. Fahrmann, Neeraj Y. Saini, Chang Chia-Chi, Ehsan Irajizad, Paolo Strati, Ranjit Nair, Luis E. Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan Iyer, Raphael Steiner, Jody Vykoukal, Ranran Wu, Jennifer B. Dennison, Loretta Nastoupil, Preetesh Jain, Michael Wang, Michael Green, Jason Westin, Viktoria Blumenberg, Marco Davila, Richard Champlin, Elizabeth J. Shpall, Partow Kebriaei, Christopher R. Flowers, Michael Jain, Robert Jenq, Christoph K. Stein-Thoeringer, Marion Subklewe, Sattva S. Neelapu, Sam Hanash
Summary: This study found that an MYC-driven polyamine signature can be used as a liquid biopsy to predict the response to anti-CD19 CAR-T therapy in patients with relapsed or refractory large B cell lymphoma. Elevated levels of acetylated polyamines in plasma were associated with non-durable response, while increased expression of spermidine synthase was prognostic for survival. A 6-marker panel consisting of acetylspermidine, diacetylspermidine, and lysophospholipids was validated as predictive of non-durable response in an independent set of patients. A polyamine centric metabolomics liquid biopsy panel has predictive value for response to CAR-T therapy in relapsed or refractory large B cell lymphoma.
CELL REPORTS MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Christoph K. Stein-Thoeringer, Neeraj Y. Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Matthias A. Fante, Sabine Schmidt, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren McDaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E. Fayad, Sairah Ahmed, Swaminathan P. Iyer, Raphael E. Steiner, Preetesh Jain, Loretta J. Nastoupil, Jason Westin, Reetakshi Arora, Michael L. Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Mueller-Tidow, Frederick L. Locke, Marco L. Davila, Richard E. Champlin, Christopher R. Flowers, Elizabeth J. Shpall, Hendrik Poeck, Sattva S. Neelapu, Michael Schmitt, Marion Subklewe, Michael D. Jain, Robert R. Jenq, Eran Elinav
Summary: Evidence suggests that the gut microbiome may influence the effectiveness of cancer immunotherapy. In a cohort of B cell lymphoma patients from Germany and the United States, it was found that the use of broad-spectrum antibiotics prior to CAR-T cell therapy was associated with negative outcomes. Additionally, certain microbiome features were found to be correlated with the survival and progression of lymphoma in these patients.
Article
Hematology
David A. Sallman, Tessa Kerre, Violaine Havelange, Xavier Poire, Philippe Lewalle, Eunice S. Wang, Jason B. Brayer, Marco L. Davila, Ine Moors, Jean-Pascal Machiels, Ahmad Awada, Erik M. Alcantar-Orozco, Rossitza Borissova, Nathalie Braun, Marie-Sophie Dheur, David E. Gilham, Caroline Lonez, Frederic F. Lehmann, Anne Flament
Summary: CYAD-01, an autologous CAR T-cell product, targeting NKG2D ligands, showed anti-leukaemic activity and was well tolerated without preconditioning. Phase 1 data support the proof-of-concept and further clinical studies are warranted to improve anti-tumour activity.
LANCET HAEMATOLOGY
(2023)
Article
Hematology
Ning Dong, Lucia Rubio Lopes-Garcia, David Vinal, Christina Bachmeier, Bijal D. Shah, Taiga Nishihori, Farhad Khimani, Marco L. Davila, Aleksandr Lazaryan, Javier Pinilla-Ibarz, Frederick L. Locke, Michael D. Jain, Julio C. Chavez
Summary: This study evaluated the outcomes of axicel and tisacel CAR-T therapy in patients with transformed nonfollicular lymphomas (tNFL), including those who received concomitant ibrutinib treatment. The results showed that CD19 CAR-T therapy had good efficacy in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (tCLL/SLL) and transformed marginal zone lymphoma (tMZL) patients, while tNFL patients were more prone to immune effector cell-associated neurologic syndrome (ICANS) compared to DLBCL/tFL patients. Summary: CD19 CAR-T therapy has favorable efficacy in tCLL/SLL and tMZL patients, but careful monitoring is needed in tNFL patients. Overall, this study provides valuable insights into the use of CAR-T therapy in different types of lymphomas.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Meeting Abstract
Hematology
Doris K. Hansen, Lauren C. Peres, Ciara L. Freeman, Omar Alexis Castaneda Puglianini, Rawan Faramand, Laura B. Oswald, Kayla M. Reid, Gabriel De Avila, Brandon J. Blue, Ariel F. Grajales-Cruz, Jose Ochoa, Alexandria Shrewsbury, Cole T. Powell, Christina Copponex, Krista H. Kottra, Rebecca Gonzalez, Jennifer M. Logue, Farhad Khimani, Hany Elmariah, Michael D. Jain, Taiga Nishihori, Hien D. Liu, Jason Brayer, Ken H. Shain, Rachid Baz, Frederick L. Locke, Melissa Alsina, Marco L. Davila
Meeting Abstract
Oncology
N. B. Figura, A. J. Sim, J. C. Chavez, B. D. Shah, F. Khimani, A. Lazaryan, M. L. Davila, C. Bachmeier, T. Nishihori, H. D. Liu, K. M. Christopherson, S. Kim, F. L. Locke, M. D. Jain, T. J. Robinson
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Hematology
Anthony C. Wood, Ariel Perez Perez, Brian Arciola, Kedar Patel, Grace Johnson, Elizabeth DiMaggio, Christina A. Bachmeier, Kayla Reid, Salvatore Carallo, Melanie H. Vargas, Rawan Faramand, Julio C. Chavez, Bijal Shah, Sameh Gaballa, Farhad Khimani, Hany Elmariah, Taiga Nishihori, Aleksandr Lazaryan, Ciara Freeman, Marco L. Davila, Frederick L. Locke, Rahul Mhaskar, Claude Bassil, Michael D. Jain
Summary: This study evaluated the outcomes of renal impairment patients receiving CAR T cell therapy for DLBCL. Results showed that renal impairment did not affect renal or survival outcomes, but patients with acute kidney injury had worse clinical outcomes.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Dae H. Lee, Michael Jain, Rawan G. Faramand, Kayla Reid, Sae Bom Lee, Salvatore Corallo, Melanie Hidalgo-Vargas, Abhishek Kumar, Sanjay Chandrasekhar, Julio Chavez, Bijal Shah, Aleksandr Lazaryan, Farhad Khimani, Taiga Nishihori, Christina Bachmeier, Frederick Locke, Guilherme Oliveira, Mohammed Alomar, Marco L. Davila