Immunotherapy: The Next Frontier in Cancer Treatment DOI Creative Commons
Naveed Shuja

Developmental medico-life-sciences, Journal Year: 2024, Volume and Issue: 1(8), P. 1 - 3

Published: Dec. 18, 2024

INTRODUCTIONOver the past decade, immunotherapy has redefined landscape for cancer treatment, providing unprecedented survival benefits across a broad swath of tumors. The ability to harness and modulate immune system transformed outcomes patients, from checkpoint inhibitors (ICIs) advanced cellular therapies, such as chimeric antigen receptor (CAR) T cells CAR macrophages (CAR-MΦ). However, these advancements have come with new challenges, variability in efficacy, toxicities, lack efficacy against immunosuppressive tumor microenvironment (TME), especially solid tumors[1]. In this editorial, we explore major advances immunotherapy, potential combination therapies CAR-MΦ, need approaches overcome evolving challenges. Immune Checkpoint Inhibitors: cancers melanoma, NSCLC, RCC, ICIs become cornerstone immunotherapy. block inhibitory receptors PD-1, PD-L1, CTLA-4, thereby enable suppression unleash effective anti-tumor response. many provided durable responses some patients survived more than five years. We landmark trials that show significant improvements overall (OS) progression-free (PFS) vs. chemotherapy metastatic refractory cancers[2]. Nevertheless, despite all advances, not respond ICIs. Resistance is due heterogeneity, evasion mechanisms, TME. addition, immune-mediated adverse events (images), including gastrointestinal, dermatologic, endocrine continue be barriers. Biomarker discovery PD-L1 expression mutational burden will increasingly important field evolves identifying most likely benefit personalized therapy minimal risk cost[3]. Cellular Therapies: CAR-T Cells Emerging Role CAR-MacrophagesHowever, are transformative; now frontier Remarkable success cells, which involve engineering express tumor-specific receptors, been shown hematologic malignancies, particularly leukemia lymphoma. Despite barriers, however, tumors still limited[4]. New CAR-MΦ emerging novel solution meet Chimeric engineered into capable targeting while modifying hostile After binds through phagocytosis, they actively engulf secreting pro-inflammatory cytokines reprogram TME immunostimulatory. addition stimulating other like natural killer (NK) also amplify responses[5]. Promising safety demonstrated by early clinical trials, those HER2-expressing can persist within tumor, physical synergize immunotherapies. Safety issues, remain, notably possibility cytokine release syndrome (CRS) macrophage activation (MAS)[6]. Macrophages' intrinsic role inflammation regulation, may provide controlled response cells. These risks being mitigated tailored strategies, IL-10 expression, ensure safe application[7]. Combination future strategies its limitations improve efficacy. preclinical models, synergistic activity anti-PD-L1 anti-CTLA-4. blockade reinvigorates exhausted remodels TME, making it hospitable sustained attack[8]. Efforts biochemical barriers equally required. Since secrete or enzymes digest extracellular matrix enhances cell infiltration persistence tumors, hypothesized could diphtheria toxin, elicits an site. Moreover, immunotherapies alone, when combined conventional radiotherapy, increase presentation, infiltration, response[9]. CONCLUSION Immunotherapy fundamentally changed how treated given who were once untreatable hope. remain promising innovation unique advantages because phagocytosing presenting antigens, reprogramming TME.A rational approach ICIs, treatments would future. Additionally, concerns addressed rigorous long-term follow-up optimize treatment strategies. As stand on brink frontier, challenge scientific community clear: needs refined expand reach, becomes mainstay care, offer cures where none existed before.

Language: Английский

Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer DOI Creative Commons

Yizhao Chen,

Qianling Xin,

Mengjuan Zhu

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, first approved CAR product, has demonstrated therapeutic potential treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach immune particularly solid highlighting feasibility using macrophages to eliminate pathogens abnormal cells.

Language: Английский

Citations

1
Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy DOI Creative Commons

Baofa Yu,

Shengwen Shao, Wenxue Ma

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217350 - 217350

Published: Nov. 1, 2024

Pancreatic cancer remains one of the most challenging malignancies to treat due its late-stage diagnosis, aggressive progression, and high resistance existing therapies. This review examines latest advancements in early detection, therapeutic strategies, with a focus on emerging biomarkers, tumor microenvironment (TME) modulation, integration artificial intelligence (AI) data analysis. We highlight promising including microRNAs (miRNAs) circulating DNA (ctDNA), that offer enhanced sensitivity specificity for early-stage diagnosis when combined multi-omics panels. A detailed analysis TME reveals how components such as cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM) contribute therapy by creating immunosuppressive barriers. also discuss interventions target these components, aiming improve drug delivery overcome evasion. Furthermore, AI-driven analyses are explored their potential interpret complex data, enabling personalized treatment strategies real-time monitoring response. conclude identifying key areas future research, clinical validation regulatory frameworks AI applications, equitable access innovative comprehensive approach underscores need integrated, outcomes pancreatic cancer.

Language: Английский

Citations

6
Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors DOI Creative Commons
Tang‐Her Jaing, Yi-Wen Hsiao, Yi-Lun Wang

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 90 - 90

Published: Jan. 31, 2025

Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors been significantly limited. The differences arise from a range difficulties linked to tumors, including an unfriendly tumor microenvironment, variability within and barriers CAR-T infiltration longevity at location. Research shows that reasons for decreased cells treating are not well understood, highlighting ongoing need strategies address these challenges. Current frequently incorporate combinatorial therapies designed boost functionality enhance their capacity effectively target tumors. However, remain testing phase necessitate additional validation assess potential benefits. CAR-NK (natural killer), CAR-iNKT (invariant natural killer T), CAR-M (macrophage) emerging as promising Recent studies highlight construction optimization cells, emphasizing overcome unique challenges posed by such hypoxia metabolic barriers. This review focuses on CAR

Language: Английский

Citations

0
Advancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer DOI Creative Commons

Lijuan Qin,

Yuan Li, Juan Liu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

Immunotherapy has revolutionized cancer treatment, offering hope for patients with otherwise treatment-resistant tumors. Among the most promising approaches are cellular therapies, particularly chimeric antigen receptor T-cell (CAR-T) therapy, which shown remarkable success in hematologic malignancies. However, application of these therapies to solid tumors, such as lung and colorectal cancers, faced significant challenges. Tumor resistance mechanisms—ranging from immune evasion, loss, checkpoint upregulation, tumor microenvironment immunosuppression—remain major obstacles. This mini-review highlights latest advancements immunotherapy, a focus on addresses mechanisms that hinder their effectiveness cancers. We examine evolution CAR-T cell well potential engineered natural killer (NK) cells macrophages treatment. The review also explores cutting-edge strategies aimed at overcoming resistance, including combination gene editing technologies, nanotechnology targeted drug delivery. By discussing molecular, cellular, microenvironmental factors contributing we aim provide comprehensive overview how challenges can be overcome, paving way more effective, personalized immunotherapies

Language: Английский

Citations

0
CAR-macrophages targets CD26 to eliminate chronic myeloid leukemia stem cells DOI Creative Commons

Jiang Guoyun,

Qin Yuefeng,

Huang Zhenglan

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 13, 2025

Abstract Background Chronic myeloid leukemia stem cells (CML-LSCs), which exhibit resistance to tyrosine kinase inhibitors (TKIs), are the leading cause of treatment failure and recurrence in chronic (CML). This highlights urgent need for novel therapies aimed at eliminating these CML-LSCs. Chimeric antigen receptor macrophages (CAR-M) not only perform phagocytosis on target but also function as antigen-presenting cells, thereby activating anti-tumor immune response.CD26 (dipeptidyl peptidase 4, DPP IV) is abundantly expressed CML-LSCs functions a tumor-specific (TSA) CAR-M treatment. The purpose this study evaluate CAR-M’s efficacy targeting CD26-positive CML develop strategy Methods CD26 was constructed using mouse-derived macrophage Raw264.7 cells. overexpressed cell lines BP210 BP210-T315I. verified confocal microscopy flow cytometry. X-ray used eliminate tumorigenicity CAR-M, safety through CCK-8, clone formation assays, animal experiments. To assess anti-leukemia ability mouse model, survival, peripheral blood white counts, infiltration liver, spleen, bone marrow (BM) were measured. Additionally, CAR-THP1 constructed, its phagocytic against NCI-H2452 confirmed by microscopy. Results We successfully validated targeted both vitro vivo. data indicate that has higher efficiency than CD26-negative CAR-M-treated mice demonstrated extended survival reduced invasion. In addition, normally express CD26. Conclusion demonstrates effectively targets phagocytizes implying with could be viable method eradicating Furthermore, our discoveries illuminate potential application treating hematological malignancies.

Language: Английский

Citations

0
CAR T Cells in Lung Cancer: Targeting Tumor-Associated Antigens to Revolutionize Immunotherapy DOI
Sattam Khulaif Alenezi

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155947 - 155947

Published: March 1, 2025

Language: Английский

Citations

0
Diverse potential of chimeric antigen receptor‐engineered cell therapy: Beyond cancer DOI Creative Commons

Lvying Wu,

Lingfeng Zhu, Jin Chen

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(4)

Published: April 1, 2025

Language: Английский

Citations

0
Exploring the potential of CAR-macrophage therapy DOI
Yongyu Shi, Xia Li, Yan Dong

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 361, P. 123300 - 123300

Published: Dec. 5, 2024

Language: Английский

Citations

2
Advancing the next generation of cancer treatment with circular RNAs in CAR-T cell therapy DOI Open Access

Sanxiong Huang,

Juling Xu,

Natalia Baran

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117753 - 117753

Published: Dec. 1, 2024

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies. However, its effectiveness against solid tumors remains constrained by challenges such as exhaustion, limited persistence, and off-target effects. These highlight critical gaps in current CAR-T cell therapeutic strategies, particularly for tumor applications. Circular RNAs (circRNAs) represent a transformative class non-coding RNAs, known their exceptional stability precise regulatory functions, positioning them promising candidates enhancing next-generation therapies. Notably, circRNAs can bridge gap between preclinical research clinical application offering innovative solutions to overcome technical hurdles improve outcomes. Despite potential, remain underexplored therapies tumors, presenting significant opportunity innovation. The mechanisms through which modulate specificity are not yet fully understood, challenges, achieving efficient targeted circRNA delivery, still need be addressed. This review highlights importance integrating into enhance specificity, minimize effects, durability. By emphasizing potential identifying key gaps, this provides roadmap advancing setting stage next generation personalized cancer treatments.

Language: Английский

Citations

1
Chimeric antigen receptor macrophages targeting c-MET(CAR-M-c-MET) inhibit pancreatic cancer progression and improve cytotoxic chemotherapeutic efficacy DOI Creative Commons

Huaijin Zheng,

Xinzhe Yang,

Nan Huang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 6, 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Macrophages are abundant in tumor microenvironment, making them an attractive target for therapeutic intervention. While current immunotherapies, including immune checkpoint inhibition (ICI) and chimeric antigen receptor T (CAR-T) cells, have shown limited efficacy pancreatic cancer, a novel approach involving macrophages (CAR-M) has, although promising, not been explored cancer. In this study, we first investigated role CAR-M cells targeting c-MET The effectiveness rationality as cancer were validated through bioinformatic analyses immunohistochemical staining samples from patients. We utilized flow cytometry bioluminescence detection methods to demonstrate specific binding phagocytic killing effect on cells. Additionally, observed process engulfing using confocal microscopy long-term fluorescence live cell imaging system. situ model transplanted into NOD/SCID mice, administered intraperitoneal injections confirm its inhibitory function Furthermore, these findings human monocyte-derived (hMDM). Bioinformatics tissue microarray revealed significantly higher expression levels tissues, compared paired peritumoral correlated with worse patient survival. engineered monocytic THP-1 line hMDM (CAR-M-c-MET). CAR-M-c-MET demonstrated highly exhibited more phagocytosis abilities than pro-inflammatory polarized control macrophages. addition, synergized various cytotoxic chemotherapeutic drugs. murine model, intraperitoneally injected rapidly migrated substantially inhibited growth, which did lead obvious side effects. Cytokine arrays mRNA sequencing showed that produced activators This study provides compelling evidence safety therapy treating results suppresses progression enhances chemotherapy. Remarkably, no discernible effects occur. Further clinical trials warranted

Language: Английский

Citations

0