The next frontier in immunotherapy: potential and challenges of CAR-macrophages

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Language: Английский

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Current advancements in cellular immunotherapy for autoimmune disease

Seminars in Immunopathology, Journal Year: 2025, Volume and Issue: 47(1)

Published: Jan. 16, 2025

The management of autoimmune diseases is currently limited by therapies that largely suppress the immune system, often resulting in partial and temporary remissions. Cellular immunotherapies offer a targeted approach redirecting cells to correct underlying autoimmunity. This review explores latest advances cellular for diseases, focusing on various strategies, such as use chimeric antigen receptor (CAR) T cells, auto-antibody (CAAR) regulatory (Tregs), tolerogenic dendritic (TolDCs). We recent preclinical studies results from clinical trials demonstrate potential these either deplete autoreactive or promote tolerance through broad selective targeting cell populations. Key challenges ensuring specificity, preventing off-target effects, improving longevity therapeutic effects are discussed. evolving landscape holds promise more durable treatment responses increased specificity disease treatment.

Language: Английский

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Immunotherapy and liver transplantation for hepatocellular carcinoma: Current and future challenges

World Journal of Transplantation, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 21, 2025

Despite existing curative options like surgical removal, tissue destruction techniques, and liver transplantation for early-stage hepatocellular carcinoma (HCC), the rising incidence mortality rates of this global health burden necessitate continuous exploration novel therapeutic strategies. This review critically assesses dynamic treatment panorama HCC, focusing specifically on burgeoning role immunotherapy in two key contexts: HCC downstaging advanced to facilitate transplant candidacy. It delves into unique immunobiology highlighting tumor-mediated immune evasion mechanisms. Analyzing diverse immunotherapeutic approaches including checkpoint inhibitors, cytokine modulators, vaccines, oncolytic viruses, antigen-targeting antibodies, adoptive cell therapy, acknowledges limitations current diagnostic markers alpha-fetoprotein glypican-3 emphasizes need biomarkers patient selection monitoring. Exploring rationale neoadjuvant adjuvant research is actively exploring safety effectiveness through ongoing clinical trials. The further explores potential benefits challenges combining transplant, careful selection, meticulous monitoring, strategies mitigate post-transplant complications. Finally, latest findings from landscape future directions management, paving way optimizing improving long-term survival patients with challenging malignancy.

Language: Английский

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Engineering innate immune cells for cancer immunotherapy

Nature Biotechnology, Journal Year: 2025, Volume and Issue: 43(4), P. 516 - 533

Published: April 1, 2025

Language: Английский

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Harnessing the evolving CRISPR/Cas9 for precision oncology

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 8, 2024

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system, a groundbreaking innovation in genetic engineering, has revolutionized our approach to surmounting complex diseases, culminating CASGEVY™ approved for sickle cell anemia. Derived from microbial immune defense mechanism, CRISPR/Cas9, characterized as precision, maneuverability and universality gene editing, been harnessed versatile tool precisely manipulating DNA mammals. In the process of applying it practice, consecutive exploitation novel orthologs variants never ceases. It's conducive understanding essentialities particularly cancer, which is crucial diagnosis, prevention, treatment. CRISPR/Cas9 used not only investigate tumorous genes functioning but also model disparate cancers, providing valuable insights into tumor biology, resistance, evasion. Upon cancer therapy, instrumental developing individual precise therapies that can selectively activate or deactivate within cells, aiming cripple growth invasion sensitize cells treatments. Furthermore, facilitates development innovative treatments, enhancing targeting efficiency reprogrammed exemplified by advancements CAR-T regimen. Beyond potent screening susceptible genes, offering possibility intervening before initiative progresses. However, despite its vast potential, application research therapy accompanied significant efficacy, efficiency, technical, safety considerations. Escalating technology innovations are warranted address these issues. system revolutionizing treatment, opening up new avenues management cancers. integration this evolving clinical practice promises era precision oncology, with targeted, personalized, potentially curative patients.

Language: Английский

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Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2243 - 2243

Published: June 17, 2024

Since the introduction of rituximab in late 1990s, significant progress has been made advancing targeted therapies for B cell lymphomas, improving patients’ chance being cured and clinicians’ therapeutic armamentarium. A better understanding disease biology pathogenic pathways, coupled with refinements immunophenotypic molecular diagnostics, have instrumental these achievements. While traditional chemotherapy remains fundamental most cases, concerns surrounding chemorefractoriness cumulative toxicities, particularly depletion hemopoietic reserve, underscore imperative personalized treatment approaches. Integrating agents, notably monoclonal antibodies, alongside yielded heightened response rates prolonged survival. notable paradigm shift is underway innovative-targeted replacing cytotoxic drugs, challenging conventional salvage strategies like stem transplantation. This review examines landscape emerging targets lymphoma cells explores innovative diffuse large (DLBCL). From Chimeric Antigen Receptor-T to more potent antibody–drug conjugates, bispecific checkpoint inhibitors, small molecules targeting intracellular each modality offers promising avenues advancement. aims furnish insights into their potential implications future DLBCL strategies.

Language: Английский

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GBM immunotherapy: Exploring molecular and clinical frontiers

Life Sciences, Journal Year: 2024, Volume and Issue: 356, P. 123018 - 123018

Published: Aug. 28, 2024

Language: Английский

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A Review of CAR T Cells and Adoptive T-Cell Therapies in Lymphoid and Solid Organ Malignancies

Medical Science Monitor, Journal Year: 2025, Volume and Issue: 31

Published: Jan. 15, 2025

Chimeric antigen receptor (CAR) T cells are genetically engineered lymphocytes that express a synthetic recognizes tumor cell surface antigen, which causes the lymphocyte to kill cell. As of December 2024, US Food and Drug Administration (FDA) approved six CAR T-cell therapies, with ten therapies commercially available globally, target CD19 B-cell maturation (BCMA) molecules indications include acute lymphoblastic leukemia (ALL), large lymphoma (LBCL), follicular lymphoma, mantle chronic lymphocytic (CLL), multiple myeloma. Pharmaceutical economic forecasts have shown global therapy market was worth USD 4.6 billion in projected 25 by 2035. However, there several challenges treating hematologic malignancies therapy, reduced treatment efficacy durability some patients, long-term adverse effects, lack effective salvage treatments, limited access due cost availability, rare association developing myeloid malignancies. A tumor-infiltrating (TIL) lifileucel, is FDA-approved for advanced melanoma. The (TCR) afamitresgene autoleucel, synovial sarcoma. results from ongoing studies clinical trials awaited solid tumors (melanoma, sarcomas, carcinomas). This article reviews recent developments adoptive including lymphoid organ

Language: Английский

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Enhancing immunotherapy efficacy with synergistic low-dose radiation in metastatic melanoma: current insights and prospects

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 30, 2025

Abstract Recent advances in oncology research have highlighted the promising synergy between low-dose radiation therapy (LDRT) and immunotherapies, with growing evidence highlighting unique benefits of combination. LDRT has emerged as a potent tool for stimulating immune system, triggering systemic antitumor effects by remodeling tumor microenvironment. Notably, demonstrates remarkable efficacy even challenging metastatic sites such liver ( uveal ) brain cutaneous ), particularly advanced melanoma stages. The increasing interest utilizing secondary uveal, mucosal, or melanomas underscores its potential combination various immunotherapies. This comprehensive review traverses journey from laboratory to clinical applications, elucidating LDRT’s immunomodulatory role on microenvironment (TIME) responses. We meticulously examine preclinical ongoing trials, throwing light prospects complementary treatment. Furthermore, we explore challenges associated integration into therapies, addressing crucial factors optimal dosage, fractionation, treatment frequency, other pharmacological agents. Considering low toxicity profile, presents compelling case application across multiple lesions, augmenting response poly-metastatic disease scenarios. convergence disciplines holds immense developing novel radiotherapy-combined modalities, paving way more effective personalized strategies beyond. Moreover, dose-related toxicities immunotherapies may be reduced synergistic amplification LDRT.

Language: Английский

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Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2795 - 2795

Published: March 20, 2025

Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the absence estrogen receptors (ER), progesterone (PR), and HER2 expression. While TNBC relatively less common, accounting for only 10–15% initial diagnosis, due to its nature, it carries a worse prognosis in comparison hormone receptor-positive counterparts. Despite significant advancements screening, treatment cancer, remains important public health burden. Following with chemotherapy, surgery, radiation, over 40% patients experience relapse within 3 years achieve least benefit from post-mastectomy radiation. The tumor microenvironment environment (TME) pivotal initiation, progression, immune evasion, resistance, prognosis. TME complex network that consists cells, non-immune soluble factors located region adjacent modulates therapeutic response differentially between TNBC. mechanisms underlying radiation resistance remain unclear, immunosuppressive has been implicated chemotherapeutic resistance. Radiation therapy (RT) known alter TME; however, changes elicited are poorly date, whether these contribute unknown. This review delves into distinct characteristics TME, explores how RT influences dynamics, examines radiosensitization, radioresistance, responses.

Language: Английский

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