Advances in CAR T Cell Therapy for Non-Small Cell Lung Cancer DOI Creative Commons

Hong Ma,

Jeeban P. Das,

Conor Prendergast

и другие.

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(11), С. 9019 - 9038

Опубликована: Ноя. 12, 2023

Since its first approval by the FDA in 2017, tremendous progress has been made chimeric antigen receptor (CAR) T cell therapy, adoptive transfer of engineered, CAR-expressing lymphocyte. CAR cells are all composed three main elements: an extracellular antigen-binding domain, intracellular signaling domain responsible for activation, and a hinge that joins these two domains. Continuous improvement CARs, now their fifth generation, particularly activation. therapy revolutionized treatment hematologic malignancies. Nonetheless, use solid tumors not attained comparable levels success. Here we review challenges achieving effective tumors, emerging have shown great promise non-small lung cancer (NSCLC). A growing number clinical trials conducted to study effect on NSCLC, targeting different types surface antigens. They include epidermal growth factor (EGFR), mesothelin (MSLN), prostate stem (PSCA), mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue (TF), protein tyrosine kinase 7 (PTK7) currently under investigation trials. The developing NSCLC other approaches enhancing efficacy discussed. Finally, provide our perspective imaging action reviewing radionuclide-based techniques, direct labeling or indirect via reporter gene.

Язык: Английский

Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma DOI Creative Commons
Ester Álvarez‐Benedicto, Zeru Tian, Sumanta Chatterjee

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Авг. 31, 2023

Abstract Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B‐cell lymphoma (BL). However, the current method of CAR production complicated and expensive, requiring collection patient blood to enrich population, ex vivo engineering/activation, quality assessment before can receive treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) produce cells in situ bypass extensive laborious process currently used. Optimized SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, CD4+ wild‐type mice. delivered Cre recombinase mRNA encoding reporter mice a lymphoreplete B model (respectively) after intravenous injection without need active targeting ligands. Moreover, increased overall survival with less aggressive form lymphoma. In addition, reduced tumor metastasis liver by increasing infiltrating lymphocytes. Overall, these results offer promising alternative pre‐clinical potential treat hematological malignancies.

Язык: Английский

Процитировано

45
Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy DOI Creative Commons
Qing Li,

Shan Geng,

Hao Luo

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 7, 2024

Abstract Colorectal cancer (CRC) remains one of the leading causes cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis CRC a testament to dysregulation these signaling cascades, which culminates in malignant transformation colonic epithelium. This review aims dissect foundational mechanisms implicated CRC, elucidate generalized principles underpinning neoplastic evolution progression. We discuss molecular hallmarks including genomic, epigenomic microbial features highlight role orchestration tumorigenic process. Concurrently, we advent targeted immune therapies assessing their impact on current clinical landscape. development has been informed deepening understanding oncogenic signaling, identification key nodes within can be exploited pharmacologically. Furthermore, explore potential integrating AI enhance precision therapeutic targeting patient stratification, emphasizing personalized medicine. In summary, our captures dynamic interplay between aberrant concerted efforts counteract changes through strategies, ultimately aiming pave way for improved prognosis treatment modalities colorectal cancer.

Язык: Английский

Процитировано

36
CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors DOI Creative Commons
Lei Peng, Giacomo Sferruzza,

Luojia Yang

и другие.

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(10), С. 1089 - 1108

Опубликована: Авг. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Язык: Английский

Процитировано

28
Translating B cell immunology to the treatment of antibody-mediated allograft rejection DOI
Peter S. Heeger,

Maria Carrera Haro,

Stanley C. Jordan

и другие.

Nature Reviews Nephrology, Год журнала: 2024, Номер 20(4), С. 218 - 232

Опубликована: Янв. 2, 2024

Язык: Английский

Процитировано

24
Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met? DOI Creative Commons
Caroline Lonez, Eytan Breman

Cells, Год журнала: 2024, Номер 13(2), С. 146 - 146

Опубликована: Янв. 12, 2024

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this other malignancies and broader patient populations. However, several limitations remain, including those associated the time-consuming highly personalized manufacturing of autologous CAR-Ts. Technologies establish "off-the-shelf" allogeneic CAR-Ts low alloreactivity currently developed, strong focus on gene-editing technologies. Although these technologies have many advantages, they also limitations, double-strand breaks in DNA safety risks as well lack modulation. As an alternative, non-gene-editing provide interesting approach support development future, possibilities fine-tuning gene expression easy development. Here, we will review different ways can be manufactured discuss which used. The biggest hurdles successful summarized, finally, overview current clinical evidence comparison its counterpart given.

Язык: Английский

Процитировано

18
Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions DOI Creative Commons

Yan Zhong,

Jingfeng Liu

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Июль 10, 2024

Abstract Cancer immunotherapy harnesses the body’s immune system to combat malignancies, building upon an understanding of tumor immunosurveillance and evasion mechanisms. This therapeutic approach reactivates anti-tumor responses can be categorized into active, passive, combined immunization strategies. Active engages recognize attack cells by leveraging host immunity with cytokine supplementation or vaccination. Conversely, passive employs exogenous agents, such as monoclonal antibodies (anti-CTLA4, anti-PD1, anti-PD-L1) adoptive cell transfers (ACT) genetically engineered chimeric antigen receptor (CAR) T NK cells, exert effects. Over past decades, CAR-T therapies have gained significant traction in oncological treatment, offering hope through their targeted approach. However, potential adverse effects associated including release syndrome (CRS), off-tumor toxicity, neurotoxicity, warrant careful consideration. Recently, CAR-NK therapy has emerged a promising alternative landscape immunotherapy, distinguished its innate advantages over modalities. In this review, we will synthesize latest research clinical advancements therapies. We elucidate benefits employing oncology critically examine developmental bottlenecks impeding broader application. Our discussion aims provide comprehensive overview current status future cancer immunotherapy.

Язык: Английский

Процитировано

17
Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase DOI Creative Commons

Junyi Shen,

Rong Hu, Anqi Lin

и другие.

EClinicalMedicine, Год журнала: 2024, Номер 73, С. 102684 - 102684

Опубликована: Июнь 20, 2024

The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following treatment is lacking.

Язык: Английский

Процитировано

15
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

и другие.

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Язык: Английский

Процитировано

10
Tumor-induced metabolic immunosuppression: Mechanisms and therapeutic targets DOI Creative Commons
Jean‐Ehrland Ricci

Cell Reports, Год журнала: 2025, Номер 44(1), С. 115206 - 115206

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

3
CAR-T cell therapy for hematological malignancies: History, status and promise DOI Creative Commons
Chao Wang, Jianpeng Wang, Shusheng Che

и другие.

Heliyon, Год журнала: 2023, Номер 9(11), С. e21776 - e21776

Опубликована: Ноя. 1, 2023

For many years, the methods of cancer treatment are usually surgery, chemotherapy and radiation therapy. Although these help to improve condition, most tumors still have a poor prognosis. In recent immunotherapy has great potential in tumor treatment. Chimeric antigen receptor T-cell (CAR-T) uses patient's own T cells express chimeric receptors. (CAR) recognizes tumor-associated antigens kills cells. CAR-T achieved good results hematological tumors. 2017, FDA approved first for B-cell acute lymphoblastic leukemia (ALL). October same year, treat lymphoma. order enhance therapeutic effect, become research focus years. The structure CAR, targets treatment, adverse reactions improvement measures during process summarized. This review is an attempt highlight possibly forgotten findings advances cell

Язык: Английский

Процитировано

22