The current socioeconomic and regulatory landscape of immune effector cell therapies DOI Creative Commons
Chiranjeevi Sainatham, Devvrat Yadav, Aravind Dilli Babu

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 4, 2024

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell (TCR) T natural killer (NK) and macrophage-based represent a transformative approach to cancer treatment, harnessing the immune system target eradicate malignant cells. CAR-T therapy, most established among these, involves engineering cells express CARs specific antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, multiple myeloma. Similarly, TCR-modified which reprogram recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for range of solid tumors. NK-cell therapies leverage NK cells' innate cytotoxicity, providing an allogeneic that avoids some immune-related complications associated with T-cell-based therapies. Macrophage-based still early stages development, focus on reprogramming macrophages stimulate response against microenvironment. Despite their promise, socioeconomic regulatory challenges hinder accessibility scalability These treatments are costly, currently exceeding $400,000 per patient, creating significant disparities access based status geographic location. The high manufacturing costs stem from personalized, labor-intensive processes harvesting, modifying, expanding patients' Moreover, logistics delivering these limit reach, particularly low-resource settings. Regulatory pathways further complicate landscape. In United States., Food Drug Administrations' (FDA) accelerated approval cell-based facilitate innovation but do not address cost-related barriers. Europe, European Medicines Agency (EMA) offers adaptive pathways, yet decentralized reimbursement systems create uneven across member states. Additionally, differing standards quality control worldwide pose hurdles global harmonization access. To expand reach multipronged is needed-streamlined frameworks, policies reduce treatment costs, international collaborations standardize manufacturing. Addressing obstacles essential make life-saving accessible broader patient population worldwide. We present literature review current landscape barriers approved standard care therapy at various levels.

Language: Английский

The next frontier in immunotherapy: potential and challenges of CAR-macrophages DOI Creative Commons
Jing Li,

Ping Chen,

Wenxue Ma

et al.

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

Citations

11
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
Are monocytes a preferable option to develop myeloid cell-based therapies for solid tumors? DOI Creative Commons

Daisy Bhatia,

Riccardo Dolcetti, Roberta Mazzieri

et al.

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

Published: March 15, 2025

Abstract In the last two decades, novel and promising cell-based therapies have populated treatment landscape for haematological tumors. However, commonly exploited T NK show limited applicability to solid This is mainly given by impaired tumor trafficking capability effector activity of these cells within a highly immunosuppressive microenvironment. Myeloid spontaneously home tumors can thus be reprogrammed and/or engineered directly attack or locally selectively deliver therapeutically relevant payloads that may improve efficacy immunotherapy against difficult-to-access context myeloid therapies, adoptive transfer monocytes has often been overshadowed infusion differentiated macrophages hematopoietic stem cell transplantation despite their therapeutic potential. Here, we summarize recent improvements benefits using tumors, current clinical applications challenges use as well some possible strategies overcome them.

Language: Английский

Citations

1
Harnessing the evolving CRISPR/Cas9 for precision oncology DOI Creative Commons
Tianye Li,

Shuiquan Li,

Yue Kang

et al.

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

Citations

7
Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies DOI Creative Commons

Kexin Ai,

Bowen Liu, Xiaomei Chen

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Nov. 5, 2024

Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address challenges sliding cells. Despite improvements from fourth next-generation cells, new include systemic toxicity continuously secreted proteins, low productivity, elevated costs. Recent research targets genetic modifications boost killing potential, metabolic interventions hinder progression, diverse combination strategies enhance therapy. Efforts reduce duration cost developing allogenic in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies platforms potential overcome limitations treating tumors. This review explores optimize therapies for tumors, focusing on enhancing overcoming restrictions. We summarize recent advances T subset selection, structural modifications, infiltration enhancement, interventions, production optimization, integration novel technologies, presenting therapeutic approaches that could improve therapy's applicability

Language: Английский

Citations

7
CAR-T therapy for ovarian cancer: Recent advances and future directions DOI
Qianling Xin,

Yizhao Chen,

Xiaojing Sun

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 226, P. 116349 - 116349

Published: June 7, 2024

Language: Английский

Citations

6
The Genetic Analysis and Clinical Therapy in Lung Cancer: Current Advances and Future Directions DOI Open Access
Angela Rina, Debora Maffeo, Francesca Minnai

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2882 - 2882

Published: Aug. 19, 2024

Lung cancer, including both non-small cell lung cancer and small remains the leading cause of cancer-related mortality worldwide, representing 18% total deaths in 2020. Many patients are identified already at an advanced stage with metastatic disease have a worsening prognosis. Recent advances genetic understanding opened new avenues for personalized treatments targeted therapies. This review examines latest discoveries genetics discusses key biomarkers, analyzes current clinical therapies based on this information. It will conclude discussion future prospects potential research directions.

Language: Английский

Citations

5
CAR-macrophage: Breaking new ground in cellular immunotherapy DOI Creative Commons

Ting Huang,

Chenqi Bei,

Zhenhua Hu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 3, 2024

Chimeric Antigen Receptor (CAR) technology has revolutionized cellular immunotherapy, particularly with the success of CAR-T cells in treating hematologic malignancies. However, have limited efficacy against solid tumors. To address these limitations, CAR-macrophages (CAR-Ms) leverage innate properties macrophages specificity and potency CAR technology, offering a novel promising approach to cancer immunotherapy. Preclinical studies shown that CAR-Ms can effectively target destroy tumor cells, even within challenging microenvironments, by exhibiting direct cytotoxicity enhancing recruitment activation other immune cells. Additionally, favorable safety profile their persistence tumors position as potentially safer more durable therapeutic options compared This review explores recent advancements including engineering strategies optimize anti-tumor preclinical evidence supporting use. We also discuss challenges future directions developing therapies, emphasizing potential revolutionize By harnessing unique macrophages, offer groundbreaking overcoming current limitations cell paving way for effective sustainable treatments.

Language: Английский

Citations

5
Macrophages as Targets in Hepatocellular Carcinoma Therapy DOI Open Access

Y. Liu,

Zhengwei Mao, Yuan Ding

et al.

Molecular Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 23(6), P. 780 - 790

Published: Feb. 2, 2024

Hepatocellular carcinoma (HCC) is a malignant tumor with complex and diverse immunosuppressive microenvironment. Tumor-associated macrophages (TAM) are an essential component of the immune TAMs typically exist in two primary states: anti-tumor M1 protumor M2 macrophages. Remarkably, possess high plasticity, enabling them to switch between different subtypes or alter their biological functions response Based on research into role occurrence development tumors, including HCC, emerging as promising targets for novel treatment strategies. In this review, we provide detailed introduction origin TAMs, elucidate interactions other cells microenvironment describe roles, characteristics, mechanisms progression HCC. Furthermore, furnish overview latest therapeutic strategies targeting TAMs.

Language: Английский

Citations

4
Potential applications of macrophages in cancer immunotherapy DOI Creative Commons
Maryam Sadri, Sahel Heidari, Arezoo Faridzadeh

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117161 - 117161

Published: July 23, 2024

Language: Английский

Citations

4