Exploring treatment options in cancer: Tumor treatment strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 17, 2024

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive remarkable transformation. Emerging fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, gene therapy. These cutting-edge not only afford personalized precise targeting, but also provide enhanced comfort potential to impede disease progression. Nonetheless, it is acknowledged that these strategies still harbour untapped for further advancement. Gaining understanding merits limitations holds promise offering novel perspectives clinical practice foundational research endeavours. In this review, we discussed different modalities, including drugs, peptide antibody cell therapy, It will detailed explanation each method, addressing their status development, challenges, solutions. The aim assist clinicians researchers in gaining deeper diverse options, enabling them carry out effective advance more efficiently.

Language: Английский

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Natural killer cells in clinical development as non-engineered, engineered, and combination therapies

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 8, 2022

Natural killer (NK) cells are unique immune effectors able to kill cancer by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for and has recently emerged with hundreds clinical trials paving the way finally achieve market authorization. Advantages cell therapies include use allogenic sources, off-the-shelf availability, no risk graft-versus-host disease (GvHD). have reached stage as ex vivo expanded differentiated non-engineered cells, chimeric antigen receptor (CAR)-engineered or CD16-engineered products, combination antibodies, priming agents, other drugs. This review summarizes recent status allogeneic cell-based hematological solid tumors, discussing main characteristics different sources used product development, their in manufacturing processes, engineering methods strategies adopted genetically modified chosen approaches therapies. A comparative analysis between NK-based non-engineered, engineered, presented, examining choices made developers regarding source targeted tumor indications, both cancers. Clinical trial outcomes discussed and, when available, assessed comparison preclinical data. Regulatory challenges approval reviewed, highlighting lack specificity requirements standardization products. Additionally, competitive landscape business field presented. offers comprehensive overview effort driven biotech pharmaceutical companies academic centers bring pivotal stages

Language: Английский

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Exploiting innate immunity for cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

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Challenges and new technologies in adoptive cell therapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 18, 2023

Abstract Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to subsequent specific enhanced T receptor (TCR)-T and chimeric antigen (CAR)-T therapies, many novel strategies cancer treatment been developed. Owing its promising outcomes, CAR-T therapy has revolutionized field ACTs, particularly hematologic malignancies. Despite these advances, still limitations in both autologous allogeneic settings, including practicality toxicity issues. To overcome challenges, researchers focused on application CAR engineering technology other types immune engineering. Consequently, several new based developed, CAR-NK, CAR-macrophage, CAR-γδT, CAR-NKT. In this review, we describe development, advantages, possible challenges aforementioned ACTs discuss current aimed at maximizing therapeutic potential ACTs. We also provide an overview various gene transduction employed immunotherapy given their importance Furthermore, possibility that capable creating a positive feedback circuit, as healthy systems do, could address flaw single type ACT, thus serve key players future immunotherapy.

Language: Английский

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Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 15, 2024

Abstract Immunotherapy has rapidly evolved in the past decades battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success certain hematologic malignancies, although they still face limitations, including high costs and toxic effects. Natural killer (NK cells), as a vital component of immune system, serve “first responders” context cancer development. In this literature review, we provide an updated understanding NK cell development, functions, their applications disease therapy. Furthermore, explore rationale for utilizing engineered therapies, such CAR-NK cells, discuss differences between CAR-T cells. We also insights into key elements strategies involved CAR design addition, highlight challenges currently encountered future directions research utilization, pre-clinical investigations ongoing clinical trials. Based on outstanding antitumor potential it is highly likely that will lead to groundbreaking advancements treatment future.

Language: Английский

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CAR-NK cells for cancer immunotherapy: recent advances and future directions

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 9, 2024

Natural Killer (NK) cells, intrinsic to the innate immune system, are pivotal in combating cancer due their independent cytotoxic capabilities antitumor response. Unlike predominant treatments that target T cell immunity, limited success of immunotherapy emphasizes urgency for innovative approaches, with a spotlight on harnessing potential NK cells. Despite tumors adapting mechanisms evade cell-induced cytotoxicity, there is optimism surrounding Chimeric Antigen Receptor (CAR) This comprehensive review delves into foundational features and recent breakthroughs comprehending dynamics cells within tumor microenvironment. It critically evaluates applications challenges associated emerging CAR-NK therapeutic strategies, positioning them as promising tools evolving landscape precision medicine. As research progresses, unique attributes offer new avenue interventions, paving way more effective precise approach treatment.

Language: Английский

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Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 11, 2025

Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy solid tumors, lethal adverse effects, high cost of autologous products, and the risk GvHD in allogeneic settings. As a potential alternative, CAR-NK can overcome most limitations provide off-the-shelf, safer, more affordable product. Although published results from preclinical clinical studies cells are promising, bottlenecks must be unlocked to maximize effectiveness therapy. These include vivo persistence, trafficking into tumor sites, modest sensitivity immunosuppressive microenvironment. In recent years, advances gene manipulation tools strategies have laid groundwork current This review will introduce existing discuss their advantages disadvantages. We also explore how these enhance therapy’s safety efficacy.

Language: Английский

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Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 4, 2022

Natural killer (NK) cells are lymphocytes with a key role in the defense against viral infections and tumor cells. Although NK classified as innate lymphoid (ILCs), under certain circumstances they exhibit adaptive memory-like features. The latter may be achieved, among others, by brief stimulation interleukin (IL)-12, IL-15 IL-18. These cytokine-induced (CIML) resemble trained immunity observed myeloid CIML undergo transcriptional, epigenetic metabolic reprogramming that, along changes expression of cell surface receptors components cytotoxic granules, responsible for their enhanced effector functions after resting period. In addition, these persist long time, which make them good candidate cancer immunotherapy. Currently, several clinical trials testing infusions to treat tumors, mostly hematological malignancies. relapse/refractory acute leukemia (AML), adoptive transfer is safe complete remissions have been observed. our review, we sought summarize current knowledge about generation molecular basis responses up-to-date results from

Language: Английский

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Engineering Induced Pluripotent Stem Cells for Cancer Immunotherapy

Cancers, Journal Year: 2022, Volume and Issue: 14(9), P. 2266 - 2266

Published: May 1, 2022

Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there critical obstacles that hinder widespread clinical applications current autologous therapies, high cost, challenging large-scale manufacturing, and inaccessibility therapy for lymphopenia patients. Therefore, it is great demand generate universal off-the-shelf products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an “unlimited supply” because their unique self-renewal properties capacity be genetically engineered. iPSCs can differentiated into different immune cells, natural killer (NK) invariant (iNKT) gamma delta (γδ T), mucosal-associated (MAIT) macrophages (Mφs). In this review, we describe iPSC-based allogeneic culture methods generating iPSC-derived (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT iPSC-Mφ), well recent advances iPSC-T iPSC-NK particularly combinations CAR-engineering. We also discuss challenges future perspectives field towards foreseeable therapy.

Language: Английский

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Immunotargeting of Cancer Stem Cells

Cancers, Journal Year: 2023, Volume and Issue: 15(5), P. 1608 - 1608

Published: March 5, 2023

The generally accepted view is that CSCs hijack the signaling pathways attributed to normal stem cells regulate self-renewal and differentiation processes. Therefore, development of selective targeting strategies for CSC, although clinically meaningful, associated with significant challenges because CSC share many important mechanisms their maintenance survival. Furthermore, efficacy this therapy opposed by tumor heterogeneity plasticity. While there have been considerable efforts target populations chemical inhibition developmental such as Notch, Hedgehog (Hh), Wnt/β-catenin, noticeably fewer attempts were focused on stimulation immune response CSC-specific antigens, including cell-surface targets. Cancer immunotherapies are based triggering anti-tumor specific activation targeted redirecting toward cells. This review CSC-directed immunotherapeutic approaches bispecific antibodies antibody-drug candidates, CSC-targeted cellular immunotherapies, immune-based vaccines. We discuss improve safety different describe current state clinical development.

Language: Английский

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