CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression DOI Creative Commons
Kristen Fousek, Junji Watanabe, Sujith K. Joseph

et al.

Leukemia, Journal Year: 2020, Volume and Issue: 35(1), P. 75 - 89

Published: March 24, 2020

Abstract Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrate remarkable efficacy in treating B-lineage acute lymphoblastic leukemia (BL-ALL), yet up to 39% of treated patients relapse with CD19(−) disease. We report that escape is associated downregulation, but preservation, targetable expression CD20 and CD22. Accordingly, we reasoned broadening the spectrum CD19CAR include both CD22 would enable them target BL-ALL while preserving their upfront efficacy. created a CD19/20/22-targeting CAR T-cell by coexpressing individual molecules on single using one tricistronic transgene. CD19/20/22CAR killed blasts from who relapsed after therapy CRISPR/Cas9 knockout primary vitro an animal model, were ineffective. At subcellular level, formed dense immune synapses cells mediated effective cytolytic complex formation, efficient serial killers single-cell tracking studies, as efficacious against CD19(+) In conclusion, independent expression, could be used salvage or front-line for recalcitrant

Language: Английский

Engineering CAR-T cells DOI Creative Commons
Cheng Zhang, Jun Li,

Jiang F. Zhong

et al.

Biomarker Research, Journal Year: 2017, Volume and Issue: 5(1)

Published: June 24, 2017

Chimeric antigen receptor redirected T cells (CAR-T cells) have achieved inspiring outcomes in patients with B cell malignancies, and are now being investigated other hematologic malignancies solid tumors. CAR-T generated by the from patients' or donors' blood. After expanded genetically modified, they reinfused into patients. However, many challenges still need to be resolved order for this technology gain widespread adoption. In review, we first discuss structure evolution of chimeric receptors. We then report on tools used production cells. Finally, address posed

Language: Английский

Citations

485
Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia DOI
Elena J. Orlando,

Xia Han,

Catherine Tribouley

et al.

Nature Medicine, Journal Year: 2018, Volume and Issue: 24(10), P. 1504 - 1506

Published: Sept. 27, 2018

Language: Английский

Citations

480
Role of pyroptosis in inflammation and cancer DOI Open Access
Wei Xiang, Feng Xie, Xiaoxue Zhou

et al.

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(9), P. 971 - 992

Published: Aug. 15, 2022

Language: Английский

Citations

431
Isolation and characterization of exosomes for cancer research DOI Creative Commons
Le Zhu, Haoting Sun, Shun Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Nov. 10, 2020

Abstract Exosomes are a subset of extracellular vesicles that carry specific combinations proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests exosomes participate in intercellular communication act as important molecular vehicles the regulation numerous physiological pathological processes, including cancer development. released by various cell types under both normal conditions, they can be found multiple bodily fluids. Moreover, carrying wide variety macromolecules provide window into altered cellular or tissue states. Their presence biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers diagnosis, prediction, surveillance. Due to their biocompatibility low immunogenicity cytotoxicity, have clinical applications development innovative therapeutic approaches. Here, we summarize recent advances technologies exosome isolation research. We outline functions regulating tumor metastasis, drug resistance, immune modulation context Finally, discuss prospects challenges exosome-based therapeutics.

Language: Английский

Citations

382
CAR-T cells: the long and winding road to solid tumors DOI Creative Commons

Maria Michela D’Aloia,

Ilaria Grazia Zizzari, Benedetto Sacchetti

et al.

Cell Death and Disease, Journal Year: 2018, Volume and Issue: 9(3)

Published: Feb. 15, 2018

Abstract Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the “next generation” cancer hallmarks. CAR-T fail to as effective in liquid for inability reach and survive microenvironment surrounding neoplastic foci. The intricate net cross-interactions occurring between tumor components, stromal immune leads an ineffective anergic status favoring evasion from host’s defenses. Our goal is hereby trace road imposed by cells, highlighting pitfalls strategies developed refined possibly overcome these hurdles.

Language: Английский

Citations

366
The Hippo signalling pathway and its implications in human health and diseases DOI Creative Commons

Minyang Fu,

Yuan Hu,

Tianxia Lan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 8, 2022

Abstract As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in regulation of numerous biological processes. Thus, substantial efforts have been made to understand upstream signals that influence activity pathway, as well its physiological functions, such cell proliferation and differentiation, organ growth, embryogenesis, tissue regeneration/wound healing. However, dysregulation can cause variety diseases, including cancer, eye cardiac pulmonary renal hepatic immune dysfunction. Therefore, therapeutic strategies target dysregulated components might be promising approaches for treatment wide spectrum diseases. Here, we review key critical functions controlled by pathway. Additionally, diseases associated with alterations potential therapies targeting will discussed.

Language: Английский

Citations

353
Lessons learned from the blockade of immune checkpoints in cancer immunotherapy DOI Creative Commons
Xiaolei Li, Changshun Shao, Yufang Shi

et al.

Journal of Hematology & Oncology, Journal Year: 2018, Volume and Issue: 11(1)

Published: Feb. 26, 2018

The advent of immunotherapy, especially checkpoint inhibitor-based has provided novel and powerful weapons against cancer. Because only a subset cancer patients exhibit durable responses, further exploration the mechanisms underlying resistance to immunotherapy in bulk is merited. Such efforts may help identify which could benefit from immune blockade. Given existence great number pathways by can escape surveillance, complexity tumor-immune system interaction, development various combination therapies, including those that combine with conventional would be necessary. In this review, we summarize current understanding blockade occurs, outline how actionable strategies derived improve clinical outcomes for patients.

Language: Английский

Citations

325
Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response DOI Creative Commons
Dongrui Wang,

Xianlin Wu,

Yingli Sun

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 19, 2022

Abstract Cancers are highly complex diseases that characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming system play critical roles in tumor initiation progression. Immunotherapy aims to reactivate antitumor overcome escape mechanisms tumors. Represented checkpoint blockade adoptive cell transfer, immunotherapy has seen tremendous success clinic, with capability induce long-term regression some tumors refractory all other treatments. Among them, blocking therapy, represented PD-1/PD-L1 inhibitors (nivolumab) CTLA-4 (ipilimumab), shown encouraging therapeutic effects treatment various tumors, such as non-small lung cancer (NSCLC) melanoma. In addition, advent CAR-T, CAR-M novel methods, entered a new era. At present, evidence indicates combination multiple methods may be one way improve effect. However, overall clinical response rate still needs improvement, which warrants development designs well discovery biomarkers can guide prescription these agents. Learning from past failure both basic research is for rational design studies future. this article, we describe efforts manipulate against discuss different targets types exploited promote

Language: Английский

Citations

310
Harnessing tumor-associated macrophages as aids for cancer immunotherapy DOI Creative Commons
Xiaolei Li, Rui Liu, Xiao Su

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Dec. 1, 2019

Abstract Cancer immunotherapies that engage immune cells to fight against tumors are proving be powerful weapons in combating cancer and becoming increasingly utilized the clinics. However, for majority of patients with solid tumors, little or no progress has been seen, presumably due lack adequate approaches can reprogram local immunosuppressive tumor milieu thus reinvigorate antitumor immunity. Tumor-associated macrophages (TAMs), which abundantly infiltrate most could contribute progression by stimulating proliferation, angiogenesis, metastasis, providing a barrier Initial TAMs-targeting strategies have shown efficacy across therapeutic modalities types both preclinical clinical studies. TAMs-targeted roughly divided into those deplete TAMs modulate activities. We here reviewed mechanisms become compromise TAMs-focused also summarized.

Language: Английский

Citations

302
Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML DOI Creative Commons
Fabiana Perna, Samuel H. Berman,

Rajesh Soni

et al.

Cancer Cell, Journal Year: 2017, Volume and Issue: 32(4), P. 506 - 519.e5

Published: Oct. 1, 2017

Highlights•We generated and annotated an extensive dataset of AML cell surface proteins•We designed algorithm to identify candidate CAR targets•We defined six criteria for combinatorial pairing identified target combinations fulfilling stringent therapySummaryChimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To potential targets myeloid leukemia (AML), we probed the surfaceome overexpressed molecules tolerable systemic expression. We integrated large transcriptomics proteomics datasets from malignant normal tissues, developed expressed stem cells, but not CD34+CD38− hematopoietic T or vital tissues. As these investigations did uncover a profile as favorable CD19, generalizable strategy efficacy safety criteria. Our findings indicate that several pairings hold great promise AML.

Language: Английский

Citations

298