keyword
https://read.qxmd.com/read/38485186/biomarkers-for-response-to-til-therapy-a-comprehensive-review
#21
REVIEW
Víctor Albarrán Fernández, Pablo Ballestín Martínez, Joachim Stoltenborg Granhøj, Troels Holz Borch, Marco Donia, Inge Marie Svane
Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients with metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical and clinical effort is required to optimize patient selection by identifying predictive biomarkers of response. This review aims to comprehensively summarize the current evidence regarding the potential impact of tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status of oncogenic driver genes, and epigenetic modifications), patient characteristics (including disease burden and location, baseline cytokines and lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure to immune checkpoint inhibitors and other anticancer therapies), phenotypic features of the transferred T cells (mainly the total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and scope of target tumor-associated antigens), and other treatment-related factors (such as lymphodepleting chemotherapy and postinfusion administration of interleukin-2)...
March 13, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38483840/particle-based-artificial-antigen-presenting-cell-systems-for-t-cell-activation-in-adoptive-t-cell-therapy
#22
REVIEW
Fei Hou, Zichao Guo, Minh Trang Ho, Yue Hui, Chun-Xia Zhao
T cell-based adoptive cell therapy (ACT) has emerged as a promising treatment for various diseases, particularly cancers. Unlike other immunotherapy modalities, ACT involves directly transferring engineered T cells into patients to eradicate diseased cells; hence, it necessitates methods for effectively activating and expanding T cells in vitro . Artificial antigen-presenting cells (aAPCs) have been widely developed based on biomaterials, particularly micro- and nanoparticles, and functionalized with T cell stimulatory antibodies to closely mimic the natural T cell-APC interactions...
March 14, 2024: ACS Nano
https://read.qxmd.com/read/38480914/advancing-rare-disease-treatment-ema-s-decade-long-insights-into-engineered-adoptive-cell-therapy-for-rare-cancers-and-orphan-designation
#23
JOURNAL ARTICLE
Maria Elisabeth Kalland, Tomas Pose-Boirazian, Gloria Maria Palomo, Frauke Naumann-Winter, Enrico Costa, Darius Matusevicius, Dinah M Duarte, Eva Malikova, Dinko Vitezic, Kristina Larsson, Armando Magrelli, Violeta Stoyanova-Beninska, Segundo Mariz
Adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has emerged as a promising approach for targeting and treating rare oncological conditions. The orphan medicinal product designation by the European Union (EU) plays a crucial role in promoting development of medicines for rare conditions according to the EU Orphan Regulation.This regulatory landscape analysis examines the evolution, regulatory challenges, and clinical outcomes of genetically engineered ACT, with a focus on CAR-T cell therapies, based on the European Medicines Agency's Committee for Orphan Medicinal Products review of applications evaluated for orphan designation and maintenance of the status over a 10-year period...
March 14, 2024: Gene Therapy
https://read.qxmd.com/read/38474415/building-a-better-defense-expanding-and-improving-natural-killer-cells-for-adoptive-cell-therapy
#24
REVIEW
Andreia Maia, Mubin Tarannum, Joana R Lérias, Sara Piccinelli, Luis Miguel Borrego, Markus Maeurer, Rizwan Romee, Mireia Castillo-Martin
Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited in vivo persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges...
March 5, 2024: Cells
https://read.qxmd.com/read/38473878/chimeric-antigen-receptor-t-cell-therapy-for-hepatocellular-carcinoma-where-do-we-stand
#25
REVIEW
Ioanna Aggeletopoulou, Maria Kalafateli, Christos Triantos
Hepatocellular carcinoma (HCC) remains a global health challenge that urgently calls for innovative therapeutic strategies. Chimeric antigen receptor T cell (CAR T) therapy has emerged as a promising avenue for HCC treatment. However, the therapeutic efficacy of CAR T immunotherapy in HCC patients is significantly compromised by some major issues including the immunosuppressive environment within the tumor, antigen heterogeneity, CAR T cell exhaustion, and the advanced risk for on-target/off-tumor toxicity...
February 23, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38468282/gene-editing-technology-to-improve-antitumor-t-cell-functions-in-adoptive-immunotherapy
#26
REVIEW
Yusuke Ito, Satoshi Inoue, Yuki Kagoya
Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties...
March 11, 2024: Inflammation and Regeneration
https://read.qxmd.com/read/38467982/development-of-immune-cell-therapy-using-t-cells-generated-from-pluripotent-stem-cells
#27
JOURNAL ARTICLE
Hiroshi Kawamoto, Kyoko Masuda, Seiji Nagano
In the field of cancer immunotherapy, the effectiveness of a method in which patient-derived T cells are genetically modified ex vivo and administered to patients has been demonstrated. However, problems remain with this method, such as (1) time-consuming, (2) costly, and (3) difficult to guarantee the quality. To overcome these barriers, strategies to regenerate T cells using iPSC technology are being pursued by several groups in the last decade. The authors have been developing a method by which specific TCR genes are introduced into iPSCs and T cells are generated from those iPSCs (TCR-iPSC method)...
2024: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/38467973/regulatory-t-cells-for-control-of-autoimmunity
#28
JOURNAL ARTICLE
Ryoji Kawakami, Shimon Sakaguchi
Regulatory T (Treg) cells, which specifically express the master transcription factor FoxP3, are indispensable for the maintenance of immunological self-tolerance and homeostasis. Their functional or numerical anomalies can be causative of autoimmune and other inflammatory diseases. Recent advances in the research of the cellular and molecular basis of how Treg cells develop, exert suppression, and maintain their function have enabled devising various ways for controlling physiological and pathological immune responses by targeting Treg cells...
2024: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/38464085/car-engineered-lymphocyte-persistence-is-governed-by-a-fas-ligand-fas-auto-regulatory-circuit
#29
Fei Yi, Tal Cohen, Natalie Zimmerman, Friederike Dündar, Paul Zumbo, Razan Eltilib, Erica J Brophy, Hannah Arkin, Judith Feucht, Michael V Gormally, Christopher S Hackett, Korbinian N Kropp, Inaki Etxeberria, Smita S Chandran, Jae H Park, Katharine C Hsu, Michel Sadelain, Doron Betel, Christopher A Klebanoff
Chimeric antigen receptor (CAR)-engineered T and NK cells can cause durable remission of B-cell malignancies; however, limited persistence restrains the full potential of these therapies in many patients. The FAS ligand (FAS-L)/FAS pathway governs naturally-occurring lymphocyte homeostasis, yet knowledge of which cells express FAS-L in patients and whether these sources compromise CAR persistence remains incomplete. Here, we constructed a single-cell atlas of diverse cancer types to identify cellular subsets expressing FASLG , the gene encoding FAS-L...
March 1, 2024: bioRxiv
https://read.qxmd.com/read/38460518/ex%C3%A2-vivo-activation-of-the-gcn2-pathway-metabolically-reprograms-t%C3%A2-cells-leading-to-enhanced-adoptive-cell-therapy
#30
JOURNAL ARTICLE
Michael St Paul, Samuel D Saibil, Meghan Kates, SeongJun Han, Scott C Lien, Rob C Laister, Kebria Hezaveh, Andreas Kloetgen, Susanne Penny, Tingxi Guo, Carlos Garcia-Batres, Logan K Smith, Douglas C Chung, Alisha R Elford, Azin Sayad, Devanand Pinto, Tak W Mak, Naoto Hirano, Tracy McGaha, Pamela S Ohashi
The manipulation of T cell metabolism to enhance anti-tumor activity is an area of active investigation. Here, we report that activating the amino acid starvation response in effector CD8+ T cells ex vivo using the general control non-depressible 2 (GCN2) agonist halofuginone (halo) enhances oxidative metabolism and effector function. Mechanistically, we identified autophagy coupled with the CD98-mTOR axis as key downstream mediators of the phenotype induced by halo treatment. The adoptive transfer of halo-treated CD8+ T cells into tumor-bearing mice led to robust tumor control and curative responses...
March 1, 2024: Cell reports medicine
https://read.qxmd.com/read/38458258/low-dose-radiotherapy-synergizes-with-irgd-anticd3-modified-t-cells-by-facilitating-t-cell-infiltration
#31
JOURNAL ARTICLE
Shujuan Zhou, Mei Zhu, Xiao Wei, Peiyuan Mu, Lijun Shen, Yan Wang, Juefeng Wan, Hui Zhang, Fan Xia, Zhen Zhang
BACKGROUND AND PURPOSE: Poor penetration of transferred T cells represents a critical factor impeding the development of adoptive cell therapy in solid tumors. We demonstrated that iRGD-antiCD3 modification promoted both T cell infiltration and activation in our previous work. Interest in low-dose radiotherapy has recently been renewed due to its immuno-stimulatory effects including T cell recruitment. This study aims to explore the synergistic effects between low-dose radiotherapy and iRGD-antiCD3-modified T cells...
March 6, 2024: Radiotherapy and Oncology
https://read.qxmd.com/read/38456768/zif-8-encapsulated-pexidartinib-delivery-via-targeted-peptide-modified-m1-macrophages-attenuates-mdsc-mediated-immunosuppression-in-osteosarcoma
#32
JOURNAL ARTICLE
Jiabao Dong, Xupeng Chai, Yucheng Xue, Shiyun Shen, Zhuo Chen, Zetao Wang, Eloy Yinwang, Shengdong Wang, Liang Chen, Fengfeng Wu, Hengyuan Li, Zehao Chen, Jianbin Xu, Zhaoming Ye, Xiongfeng Li, Qian Lu
Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically...
March 8, 2024: Small
https://read.qxmd.com/read/38451195/therapeutic-targeting-of-tim-4-l-with-engineered-t-cells-for-acute-myeloid-leukemia
#33
JOURNAL ARTICLE
Brandon Cieniewicz, Edson Oliveira, Mike Saxton, Damoun Torabi, Ankit Bhatta, Phanidhar Kukutla, Alexander Arballo, Zhuo Yang, Bi Yu, Maria Fate, Hongxiu Ning, Lawrence Corey, Abhishek Maiti, Daniel Corey
PURPOSE: Disruption of lipid bilayer asymmetry is a common feature observed in cancer cells and offers novel routes for therapeutic targeting. We utilized the natural immune receptor TIM-4 to interrogate for loss of plasma membrane phospholipid polarity in primary acute myelogenous leukemia (AML) samples and evaluated the anti-leukemic activity of TIM-4-L-directed T cell therapy in preclinical AML models. METHODS: We performed FACs analysis on 33 primary AML bone marrow specimens and correlated TIM-4-L expression frequency and intensity with molecular disease characteristics...
March 7, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38450972/development-and-characterization-of-a-cell-donor-registry-for-virus-specific-t-cell-manufacture-in-a-blood-bank
#34
JOURNAL ARTICLE
Francesc Rudilla, María Paz Carrasco-Benso, Helena Pasamar, María López-Montañés, María Andrés-Rozas, Maria Tomás-Marín, Desirée Company, Cristina Moya, Luis Larrea, Manuel Guerreiro, Pere Barba, Cristina Arbona, Sergio Querol
Adoptive cell therapy using virus-specific T cells (VST) is a strategy for treating common opportunistic viral infections after transplantation, particularly when these infections do not resolve through antiviral drug therapy. The availability of third-party healthy donors allows for the immediate use of cells for allogeneic therapy in cases where patients lack an appropriate donor. Here, we present the creation of a cell donor registry of human leukocyte antigen (HLA)-typed blood donors, REDOCEL, a strategic initiative to ensure the availability of compatible cells for donation when needed...
March 2024: HLA
https://read.qxmd.com/read/38447573/neutrophil-profiling-illuminates-anti-tumor-antigen-presenting-potency
#35
JOURNAL ARTICLE
Yingcheng Wu, Jiaqiang Ma, Xupeng Yang, Fang Nan, Tiancheng Zhang, Shuyi Ji, Dongning Rao, Hua Feng, Ke Gao, Xixi Gu, Shan Jiang, Guohe Song, Jiaomeng Pan, Mao Zhang, Yanan Xu, Shu Zhang, Yihui Fan, Xiaoying Wang, Jian Zhou, Li Yang, Jia Fan, Xiaoming Zhang, Qiang Gao
Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification...
February 28, 2024: Cell
https://read.qxmd.com/read/38446885/machine-learning-predictions-of-t-cell-antigen-specificity-from-intracellular-calcium-dynamics
#36
JOURNAL ARTICLE
Sébastien This, Santiago Costantino, Heather J Melichar
Adoptive T cell therapies rely on the production of T cells with an antigen receptor that directs their specificity toward tumor-specific antigens. Methods for identifying relevant T cell receptor (TCR) sequences, predominantly achieved through the enrichment of antigen-specific T cells, represent a major bottleneck in the production of TCR-engineered cell therapies. Fluctuation of intracellular calcium is a proximal readout of TCR signaling and candidate marker for antigen-specific T cell identification that does not require T cell expansion; however, calcium fluctuations downstream of TCR engagement are highly variable...
March 8, 2024: Science Advances
https://read.qxmd.com/read/38441967/cd8-t-cells-sustain-antitumor-response-by-mediating-crosstalk-between-adenosine-a2a-receptor-and-glutathione-gpx4
#37
JOURNAL ARTICLE
Siqi Chen, Jie Fan, Ping Xie, Jihae Ahn, Michelle Fernandez, Leah K Billingham, Jason Miska, Jennifer D Wu, Derek A Wainwright, Deyu Fang, Jeffrey A Sosman, Yong Wan, Yi Zhang, Navdeep S Chandel, Bin Zhang
Antitumor responses of CD8+ T cells are tightly regulated by distinct metabolic fitness. High levels of glutathione (GSH) are observed in the majority of tumors contributing to cancer progression and treatment resistance in part by preventing glutathione peroxidase 4 (GPX4) dependent ferroptosis. Here, we show the necessity of the adenosine A2A receptor (A2AR) signaling and the glutathione (GSH)-GPX4 axis in orchestrating metabolic fitness and survival of functionally competent CD8+ T cells. Activated CD8+ T cells treated ex vivo with simultaneous inhibition of A2AR and lipid peroxidation acquire a superior capacity to proliferate and persist in vivo, demonstrating a translatable means to prevent ferroptosis in adoptive cell therapy (ACT)...
March 5, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38438220/immunometabolic-maladaptations-to-the-tumor-microenvironment
#38
JOURNAL ARTICLE
Emma S Hathaway, Erin Q Jennings, Jeffrey C Rathmell
Tumors consist of cancer cells and a wide range of tissue resident and infiltrating cell types. Tumor metabolism, however, has largely been studied on whole tumors or cancer cells and the metabolism of infiltrating immune cells remains poorly understood. It is now clear from a range of analyses and metabolite rescue studies that metabolic adaptations to the tumor microenvironment (TME) directly impede T-cell and macrophage effector functions. The drivers of metabolic adaptation to the TME and metabolic immune suppression include depletion of essential nutrients, accumulation of waste products or immune suppression metabolites, and metabolic signaling through altered posttranslational modifications...
March 4, 2024: Cold Spring Harbor Perspectives in Medicine
https://read.qxmd.com/read/38437712/microfluidic-based-preparation-of-artificial-antigen-presenting-gel-droplets-for-integrated-and-minimalistic-adoptive-cell-therapy-strategies
#39
JOURNAL ARTICLE
Yishen Tian, Wei Chen, Guangshi Du, Jie Gao, Youbo Zhao, Zhuli Wang, Min Su, Rong Hu, Feng Han
Adoptive T-cell transfer for cancer therapy is limited by the inefficiency of in vitro T-cell expansion and the ability of in vivo T-cells to infiltrate tumors. The construction of multifunctional artificial antigen-presenting cells is a promising but challenging approach to achieve this goal. In this study, a multifunctional artificial antigen-presenting gel droplet (AAPGD) was designed. Its surface provides regulated T-cell receptor stimulation and co-stimulation signals and is capable of slow release of mitogenic cytokines and collagen mimetic peptide (CMP)...
March 4, 2024: Biofabrication
https://read.qxmd.com/read/38433349/the-progress-and-prospects-of-immune-cell-therapy-for-the-treatment-of-cancer
#40
REVIEW
Jia Han, Bowen Zhang, Senyu Zheng, Yuan Jiang, Xiaopeng Zhang, Kaiyun Mao
Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered "living drugs," and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies...
2024: Cell Transplantation
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