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)
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
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)
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.
Article
Biochemistry & Molecular Biology
Ruediger Klapdor, Shuo Wang, Michael A. Morgan, Katharina Zimmermann, Jens Hachenberg, Hildegard Buening, Thilo Doerk, Peter Hillemanns, Axel Schambach
Summary: Ovarian cancer stem cells with chemoresistance contribute to tumor recurrence, leading to poor survival rates. Targeting CD44 using CAR immunotherapy demonstrates potent cytotoxic activity against CD44-positive ovarian cancer cells. Furthermore, combined treatment of CD44-targeted therapy and cisplatin shows higher anti-tumor activity compared to sequential treatment.
Review
Immunology
Christopher Schorr, Fabiana Perna
Summary: Acute Myeloid Leukemia (AML) is an aggressive malignancy with limited therapeutic options. CAR T-cell therapy for AML faces challenges due to lack of target antigens, clonal heterogeneity, and immunosuppressive bone marrow. This study provides an updated overview of AML targets and clinical trials with CAR T-cells, serving as a potential guide for adoptive cellular therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rodrigo C. C. De Marco, Hector J. J. Monzo, Paivi M. Ojala
Summary: With the continuous advancements in immunotherapy and precision medicine, adoptive cell therapy (ACT) has emerged as a new treatment approach in oncology. Chimeric antigen receptor (CAR) T cells, genetically modified lymphocytes, have shown promising results in targeting and killing cancer cells. Commercialization of CAR T cell therapy has paved the way for future bright developments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Kaveh Hadiloo, Siavash Taremi, Mahmood Heidari, Abdolreza Esmaeilzadeh
Summary: Adoptive cell therapy, particularly using chimeric antigen receptor T cells, has shown success in cancer treatment. However, due to limitations in treating solid cancers and harmful adverse effects, researchers are exploring alternative cell therapies, such as CAR macrophage cells, to improve treatment outcomes.
BIOMARKER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Renee Poels, Esther Drent, Roeland Lameris, Afroditi Katsarou, Maria Themeli, Hans J. van der Vliet, Tanja D. de Gruijl, Niels W. C. J. van de Donk, Tuna Mutis
Summary: iNKT cells armed with CD38 and BCMA-CARs effectively eliminate MM cells without compromising their TCR-mediated cytotoxicity. These CAR iNKT cells show promising therapeutic potential with minimal impact on normal hematopoietic cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Alexander Shimabukuro-Vornhagen, Boris Boll, Peter Schellongowski, Sandrine Valade, Victoria Metaxa, Elie Azoulay, Michael von Bergwelt-Baildon
Summary: CAR T-cell therapy, a promising immunotherapeutic treatment, has shown high response rates and long-term remissions in hematologic malignancies. However, severe life-threatening toxicities such as cytokine release syndrome and neurotoxicity may occur, requiring rapid and aggressive medical treatment in the intensive care unit.
CA-A CANCER JOURNAL FOR CLINICIANS
(2022)
Review
Oncology
Ying Gong, Roel G. J. Klein Wolterink, Jianxiang Wang, Gerard M. J. Bos, Wilfred T. V. Germeraad
Summary: NK cells, especially CAR-NK cells, play a crucial role in cancer treatment. Advances in CAR-NK technology show promising potential in efficiently targeting cancer cells with reduced side effects. These developments contribute to improving cancer treatment strategies.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
P. Connor Johnson, Caron Jacobson, Alisha Yi, Mahmoud R. Gaballa, Nora Horick, Dustin J. Rabideau, Kevin Lindell, Gabriel D. DePinho, Areej R. El-Jawahri, Matthew J. Frigault
Summary: A retrospective analysis of 235 patients receiving CAR T-cell therapy found that bridging therapy use was not associated with differences in overall response, complete response rate, or progression-free survival, but was associated with worse overall survival. Additional poor prognostic factors may contribute to this association, highlighting the need for innovative bridging therapy regimens for these patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Hui Zhang, Pengfei Wang, Zhuoyan Li, Yingyi He, Wenting Gan, Hua Jiang
Summary: The study tested the safety and efficacy of anti-CLL1 CAR T-cell therapy in pediatric patients with R/R-AML, showing promising results with a high rate of complete remission and minimal residual disease negativity in patients. The therapy was well tolerated with low-grade and manageable adverse events, indicating the potential of autologous anti-CLL1 CAR T-cell therapy as a safe and efficient treatment option for children with R/R-AML. Further investigation is warranted to explore its full potential.
CLINICAL CANCER RESEARCH
(2021)
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
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
Immunology
Kathleen M. E. Gallagher, Mark B. Leick, Rebecca C. Larson, Trisha R. Berger, Katelin Katsis, Jennifer Y. Yam, Marcela Maus
Summary: Breakthrough cases among vaccinated individuals highlight the importance of long-term immunity against SARS-CoV-2 and its variants. Antibody levels and anti-spike T-cell responses decrease over time and are lower in those vaccinated with BNT162b2 compared to mRNA-1273. T-cell responses to variants remain relatively unaffected.
CLINICAL INFECTIOUS DISEASES
(2022)
Letter
Oncology
Joan How, Kathleen M. E. Gallagher, Yiwen Liu, Katelin Katsis, Eva L. Elder, Rebecca C. Larson, Mark B. Leick, Donna Neuberg, Marcela V. Maus, Gabriela S. Hobbs
Article
Multidisciplinary Sciences
Julia Joung, Paul C. Kirchgatterer, Ankita Singh, Jang H. Cho, Suchita P. Nety, Rebecca C. Larson, Rhiannon K. Macrae, Rebecca Deasy, Yuen-Yi Tseng, Marcela Maus, Feng Zhang
Summary: This study identifies several genes associated with tumor resistance to T cell cytotoxicity through a genome-scale CRISPR activation screen. Overexpression of these candidate genes, including MCL1, JUNB, and B3GNT2, confers resistance to T cell killing in various cancer cell types and mouse xenografts. Mechanistically, MCL1 and JUNB modulate the mitochondrial apoptosis pathway, while B3GNT2 disrupts interactions between tumor and T cells, leading to reduced T cell activation. Inhibition of these candidate genes sensitizes tumor models to T cell cytotoxicity.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Hematology
Marcela Maus
Summary: Genetically modified immune effector cells (IECs) hold promise as a new type of therapeutic for hematologic malignancies, but their potential to increase the risk of secondary cancers is unclear. This study found no increased risk of secondary cancers in over 1000 patient-years of follow-up across multiple clinical trials of genetically modified IECs for cancer.
Editorial Material
Oncology
Mahmoud R. Gaballa, Marcela Maus
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Kimberly R. Hagel, Rand Arafeh, Sydney Gang, Taylor E. Arnoff, Rebecca C. Larson, John G. Doench, Nathan D. Mathewson, Kai W. Wucherpfennig, Marcela Maus, William C. Hahn
Summary: This study uncovers multiple antigen-dependent and independent mechanisms of CAR T-cell evasion by pancreatic cancer, including the loss of genes involved in GPI-anchor biosynthesis and attachment pathway and genes that regulate tumor transcriptional responses. The identification of these resistance mechanisms provides insights into the landscape of tumor cell intrinsic resistance and potential approaches to improve CAR T-cell therapy efficacy in pancreatic cancer.
Review
Multidisciplinary Sciences
Darrell J. Irvine, Marcela V. Maus, David J. Mooney, Wilson W. Wong
Summary: Immune cell therapy is a promising approach to treating diseases, especially cancer, by engineering immune cells to recognize and respond to specific conditions. This therapy has already been approved for clinical use and continues to be developed and tested in various applications.
News Item
Biochemistry & Molecular Biology
Zachariah DeFilipp, Marcela V. Maus
Summary: The composition of the intestinal microbiome can predict clinical outcomes of CAR-T cell therapy for lymphoma, informing microbiota-based interventions.
Editorial Material
Oncology
Mark B. B. Leick, Marcela V. V. Maus
Summary: Plasma cell-free DNA analysis is an effective liquid biopsy for evaluating circulating tumor DNA in cancer treatment. A recent study shows that cell-free DNA can also provide information on expansion kinetics and tumor-infiltration patterns in patients receiving chimeric antigen receptor T cells. Together with circulating tumor DNA, it offers valuable prognostic insights into intratumoral dynamics.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Alexandra L. Pourzia, Michael L. Olson, Stefanie R. Bailey, Angela C. Boroughs, Aditi Aryal, Jeremy Ryan, Marcela V. Maus, Anthony Letai
CELL DEATH & DISEASE
(2023)
Review
Immunology
Marie-Noelle Kronig, Marc Wehrli, Diego Salas-Benito, Marcela V. Maus
Summary: Digestive tract cancers, especially pancreatic cancer, have high incidence, prevalence, and mortality rates, and current immunotherapy options are limited. Cellular immunotherapy, specifically CAR T-cell therapy, has shown promising results in hematological malignancies and there is interest in translating this success to solid malignancies such as DTC. This review focuses on the advances and hurdles of CAR T-cell therapy in DTC.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biotechnology & Applied Microbiology
Magdi Elsallab, Marcela V. Maus
Summary: Chimeric antigen receptor (CAR) T cells are revolutionizing the treatment of hematological malignancies. The current autologous and central manufacturing approach presents challenges in meeting the growing demand. Distributed manufacturing with advanced technologies is crucial to increase capacity and ensure uniform product quality. Expanded role of accreditation bodies and regulatory amendments are also necessary to support this model.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yi Lin, Noopur S. Raje, Jesus G. Berdeja, David S. Siegel, Sundar Jagannath, Deepu Madduri, Michaela Liedtke, Jacalyn Rosenblatt, Marcela V. Maus, Monica Massaro, Fabio Petrocca, Ashish Yeri, Olivia Finney, Andrea Caia, Zhihong Yang, Nathan Martin, Timothy B. Campbell, Julie Rytlewski, Jaymes Fuller, Kristen Hege, Nikhil C. Munshi, James N. Kochenderfer
Summary: This study conducted a post hoc analysis of the use of Idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma and found that it is safe and well-tolerated, with a positive impact on response rates. Additionally, the study identified a correlation between the state of T cells and durable responses.
Review
Biotechnology & Applied Microbiology
Marco Ruella, Felix Korell, Patrizia Porazzi, Marcela V. Maus
Summary: Chimeric antigen receptor (CAR)-T cells have shown great potential in treating blood cancers, but resistance to this therapy remains a challenge. This review summarizes the mechanisms of resistance to CAR-T cell immunotherapy, including CAR-T cell dysfunction, tumor resistance, and the immunosuppressive tumor microenvironment. It also discusses current research strategies to overcome these resistance mechanisms.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Hematology
Akshay Sharma, Stephanie Farnia, Folashade Otegbeye, Amy Rinkle, Jugna Shah, Nirali N. Shah, Saar Gill, Marcela V. Maus
Summary: As cellular and genetic therapies move from theory to practice, it has become clear that there are conflicting and imprecise terminologies to describe these novel therapeutic products. Standardization of the nomenclature is crucial for regulatory framework, training programs, accessibility decisions, and reimbursement consistency.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)