Article
Oncology
Maxwell Y. Lee, Yvette Robbins, Cem Sievers, Jay Friedman, Houssein Abdul Sater, Paul E. Clavijo, Nancy Judd, Edward Tsong, Chris Silvin, Patrick Soon-Shiong, Michelle R. Padget, Jeffrey Schlom, James Hodge, Christian Hinrichs, Clint Allen
Summary: The study demonstrates that resistance to T-cell killing in heterogeneous tumors can be overcome by using PD-L1 CAR-engineered NK cells, preventing clonal selection of T cell-resistant tumor cells and promoting PD-L1-dependent killing by PD-L1 t-haNKs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
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)
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
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
Cell Biology
Chiara Donini, Ramona Rotolo, Alessia Proment, Massimo Aglietta, Dario Sangiolo, Valeria Leuci
Summary: The term cancer stem cells (CSCs) refers to tumor cells with stemness features that may contribute to chemo-resistance and disease relapses, with potential susceptibility to immune system recognition and targeting. Cellular immunotherapies, including those using chimeric antigen receptors (CAR) for genetic redirection, show promise for selective elimination of CSC subsets in different tumor settings. Preclinical studies support the potential targeting of CSCs by cellular immunotherapies, with ongoing clinical studies and new opportunities for T and non-T antitumor lymphocytes.
Article
Pharmacology & Pharmacy
Jiaxing Tang, Yan Zou, Long Li, Fengping Lu, Hongtao Xu, Pengxuan Ren, Fang Bai, Gabriele Niedermann, Xuekai Zhu
Summary: The study showed that small molecules targeting adenosine receptors, like BAY 60-6583, can significantly increase cytokine secretion of CD133- or HER2-specific CAR T cells, enhance the cytotoxicity and proliferation of CAR T cells, and facilitate the anti-tumor activities of anti-HER2 CAR T cells in a xenograft mouse model. The data suggest that BAY 60-6583 upregulates T cell functions through a mechanism independent of the adenosine A2b receptor.
FRONTIERS IN PHARMACOLOGY
(2021)
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
Bernice Ling Zhi Oh, Louis Wei Yong Chan, Louis Yi Ann Chai
Summary: The ideal strategy to fight against invasive fungal infections is to weaken the pathogens through antimicrobial therapy and strengthen the host immunity. Natural killer (NK) cells are efficient innate executioners that can kill both tumor cells and pathogens, making them attractive for adoptive cellular therapy against invasive fungal infections. Recent advances in ex vivo NK cell activation and genetic engineering have provided an opportunity to utilize NK cells as a key component in a multipronged strategy against these infections.
FRONTIERS IN IMMUNOLOGY
(2023)
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
Oncology
Sophia Stock, Mohamed-Reda Benmebarek, Anna-Kristina Kluever, Diana Darowski, Christian Jost, Kay-Gunnar Stubenrauch, Joerg Benz, Anne Freimoser-Grundschober, Ekkehard Moessner, Pablo Umana, Marion Subklewe, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: This study developed a P329G-directed CAR T cell that can selectively bind with specific mutated antibodies, demonstrating significant in vitro and in vivo effector functions in different types of solid tumor models. This opens up possibilities for further clinical translation.
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
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
Cardiac & Cardiovascular Systems
Anjali Rao, Andrew Stewart, Mahmoud Eljalby, Praveen Ramakrishnan, Larry D. Anderson Jr, Farrukh T. Awan, Alvin Chandra, Srilakshmi Vallabhaneni, Kathleen Zhang, Vlad G. Zaha
Summary: Chimeric antigen receptor T-cell (CAR T) therapy is a personalized treatment that has revolutionized the treatment of hematologic malignancies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy, which can lead to cardiovascular complications. There is currently a lack of standardized guidelines for managing these complications.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
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
Oncology
Ann Byrne, Peter Savas, Sneha Sant, Ran Li, Balaji Virassamy, Stephen J. Luen, Paul A. Beavis, Laura K. Mackay, Paul J. Neeson, Sherene Loi
NATURE REVIEWS CLINICAL ONCOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Amanda J. Oliver, Phillip K. Darcy, Joseph A. Trapani, Michael H. Kershaw, Clare Y. Slaney
Summary: Cancer tissue is heterogeneous and tumor microenvironment cells can communicate with each other to influence their function. Moreover, tumors located remotely from each other can engage in cross-talk that can influence their responsiveness to various therapies. Communication between cancer cells and immune cells can lead to immunosuppression.
Article
Immunology
Simone Nussing, Imran G. House, Conor J. Kearney, Amanda X. Y. Chen, Stephin J. Vervoort, Paul A. Beavis, Jane Oliaro, Ricky W. Johnstone, Joseph A. Trapani, Ian A. Parish
JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Junyun Lai, Sherly Mardiana, Imran G. House, Kevin Sek, Melissa A. Henderson, Lauren Giuffrida, Amanda X. Y. Chen, Kirsten L. Todd, Emma Petley, Jack D. Chan, Emma M. Carrington, Andrew M. Lew, Benjamin J. Solomon, Joseph A. Trapani, Katherine Kedzierska, Maximilien Evrard, Stephin J. Vervoort, Jason Waithman, Phillip K. Darcy, Paul A. Beavis
Editorial Material
Oncology
Jack D. Chan, Paul A. Beavis, Phillip K. Darcy
Editorial Material
Biotechnology & Applied Microbiology
Amanda X. Y. Chen, Imran G. House, Paul A. Beavis, Phillip K. Darcy
Article
Oncology
Peter Kar Han Lau, Carleen Cullinane, Susan Jackson, Rachael Walker, Lorey K. Smith, Alison Slater, Laura Kirby, Riyaben P. Patel, Bianca von Scheidt, Clare Y. Slaney, Grant A. McArthur, Karen E. Sheppard
Summary: The combination of adoptive cell transfer (ACT) with BRAF-MEK and CDK4/6 inhibitors has shown to be highly efficacious against BRAF(V600) melanoma, providing prolonged and deep anti-tumor responses. This study offers additional pre-clinical evidence to support the combination of BRAF-MEK-CDK4/6 inhibitors and ACT in clinical trials.
Editorial Material
Cell Biology
Amanda X. Y. Chen, Emily B. Derrick, Paul A. Beavis, Imran G. House
Summary: In a recently published article, Melenhorst et al. conducted a longitudinal analysis on CAR T cells isolated from patients over a 10-year period after therapy, and found expansion of a long-lived CD4(+) CAR T-cell population with a cytotoxic phenotype.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Editorial Material
Oncology
Evan G. Pappas, Michael H. Kershaw, Clare Y. Slaney
Article
Oncology
Fernando Souza-Fonseca-Guimaraes, Gustavo R. Rossi, Laura F. Dagley, Momeneh Foroutan, Timothy R. McCulloch, Jumana Yousef, Hae-Young Park, Jennifer H. Gunter, Paul A. Beavis, Cheng-Yu Lin, Soroor Hediyeh-Zadeh, Tania Camilleri, Melissa J. Davis, Nicholas D. Huntington
CANCER IMMUNOLOGY RESEARCH
(2022)
Review
Oncology
Daniela G. M. Tantalo, Amanda J. Oliver, Bianca von Scheidt, Aaron J. Harrison, Scott N. Mueller, Michael H. Kershaw, Clare Y. Slaney
Summary: Immunotherapy has identified adoptive cell transfer as a promising approach for treating cancers, generating cancer reactive CAR T cells through genetic modification to target tumor-associated antigens. The ability of CAR T cells to respond against disease depends on their phenotypes, with current interest in generating ideal phenotypes for optimal antitumor activity through manipulation of culture conditions and genetic makeups.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Jack D. Chan, Junyun Lai, Clare Y. Slaney, Axel Kallies, Paul A. Beavis, Phillip K. Darcy
Summary: The differentiation status of tumor-specific T cells greatly impacts their anti-tumor activity, with less differentiated T cells showing better therapeutic effects due to their enhanced expansion and long-term persistence. Adoptive transfer of T cells with stem-like memory or precursor phenotype is associated with improved therapeutic outcomes in cancer patients. Advances in understanding T cell differentiation at the epigenetic and transcriptional levels have led to the development of novel methods for generating more persistent and functional tumor-specific T cells.
NATURE REVIEWS IMMUNOLOGY
(2021)
Article
Immunology
Jack D. Chan, Bianca von Scheidt, Bijun Zeng, Amanda J. Oliver, Ashleigh S. Davey, Aesha Ali, Ranjeny Thomas, Joseph A. Trapani, Phillip K. Darcy, Michael H. Kershaw, Riccardo Dolcetti, Clare Y. Slaney
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2020)
