ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights DOI Creative Commons
Alaa M. Ali, John F. DiPersio

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 5, 2024

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy solid tumors, safety concerns related to toxicity, and logistical challenges manufacturing scalability. This review critically examines latest advancements aimed at overcoming these obstacles, highlighting innovations CAR engineering, novel targeting strategies, improvements delivery persistence within tumor microenvironment. We also discuss development allogeneic T cells as off-the-shelf therapies, strategies mitigate adverse effects, integration with other therapeutic modalities. comprehensive analysis underscores synergistic potential enhance safety, efficacy, accessibility providing a forward-looking perspective on their evolutionary trajectory cancer treatment.

Язык: Английский

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

74
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

53
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

50
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

28
Colorectal cancer: Recent advances in management and treatment DOI Open Access

Hiba Fadlallah,

Jad El Masri,

Hiam Fakhereddine

и другие.

World Journal of Clinical Oncology, Год журнала: 2024, Номер 15(9), С. 1136 - 1156

Опубликована: Авг. 29, 2024

Colorectal cancer (CRC) is the third most common worldwide, and second cause of cancer-related death. In 2020, estimated number deaths due to CRC was approximately 930000, accounting for 10% all worldwide. Accordingly, there a vast amount ongoing research aiming find new improved treatment modalities that can potentially increase survival decrease overall morbidity mortality. Current management strategies include surgical procedures resectable cases, radiotherapy, chemotherapy, immunotherapy, in addition their combination, non-resectable tumors. Despite these options, remains incurable 50% cases. Nonetheless, significant improvements techniques have allowed approaches be frequently updated, leading availability drugs therapeutic strategies. This review summarizes recent CRC, with special emphasis on are currently being studied great potential improve prognosis lifespan patients CRC.

Язык: Английский

Процитировано

26
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

26
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

24
Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination DOI
Zhaokai Zhou, Yumiao Mai, Ge Zhang

и другие.

Cancer Letters, Год журнала: 2024, Номер 598, С. 217079 - 217079

Опубликована: Июнь 25, 2024

Язык: Английский

Процитировано

21
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

20
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

20