Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.

IF 13.5 1区 医学 Q1 HEMATOLOGY
Yuqian Wang, Cheng Jiang, Huiling Zhou, Rui Han
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引用次数: 0

Abstract

This review introduces a paradigm-shifting concept of Dual Distinct Immunotherapy (DDI), which strategically integrates two distinct immunotherapeutic modalities to overcome the limitations of current monotherapies and dual immune checkpoint inhibitor (ICI) combinations. The concept of DDI extends beyond traditional ICI combinations to encompass various innovative pairings: ICIs with oncolytic viruses (OVs), adoptive cell therapies (CAR-T/TIL), cancer vaccines, or cytokine therapies. These combinations demonstrate unique synergistic mechanisms and enhanced therapeutic potential through multi-faceted immune activation. Significantly, this work advances the field by analyzing potential third-agent sensitizers to complement DDI strategies. We systematically evaluate emerging candidates including PCNA inhibitors, HDAC inhibitors, and carbonic anhydrase inhibitors, focusing on their ability to modulate the tumor microenvironment and enhance immunotherapy responses. This "DDI + 1" approach targets alternative pathways to overcome resistance mechanisms and expand treatment efficacy to traditionally immunotherapy-resistant cancers. Through comprehensive analysis of preclinical evidence and ongoing clinical trials, we address critical challenges in immunotherapy, including primary and acquired resistance, cold tumor conversion, and pathway exhaustion. The review synthesizes current findings while proposing innovative solutions and future research directions. Our framework demonstrates how strategic integration of multiple immune-based approaches can significantly improve therapeutic outcomes across diverse cancer types, potentially revolutionizing cancer treatment paradigms. This concept of DDI, enhanced by rational third-agent selection, represents a promising direction for addressing urgent clinical needs in oncology. By establishing a theoretical foundation for this approach, we aim to guide future research and clinical applications in cancer immunotherapy.

转化癌症免疫治疗:整合不同的基于免疫的方法作为重新定义的双重免疫治疗与潜在的第三致敏剂。
这篇综述介绍了双重不同免疫治疗(DDI)的范式转换概念,它战略性地整合了两种不同的免疫治疗方式,以克服当前单一治疗和双重免疫检查点抑制剂(ICI)联合治疗的局限性。DDI的概念超越了传统的ICI组合,包括各种创新的配对:ICI与溶瘤病毒(OVs)、过继细胞疗法(CAR-T/TIL)、癌症疫苗或细胞因子疗法。这些组合通过多方面的免疫激活显示出独特的协同机制和增强的治疗潜力。值得注意的是,这项工作通过分析潜在的第三剂增敏剂来补充DDI策略,从而推动了该领域的发展。我们系统地评估了新兴的候选药物,包括PCNA抑制剂、HDAC抑制剂和碳酸酐酶抑制剂,重点关注它们调节肿瘤微环境和增强免疫治疗反应的能力。这种“DDI + 1”方法针对替代途径,以克服耐药机制并扩大对传统免疫治疗耐药癌症的治疗效果。通过综合分析临床前证据和正在进行的临床试验,我们解决了免疫治疗中的关键挑战,包括原发性和获得性耐药、冷肿瘤转化和途径衰竭。这篇综述综合了目前的研究结果,同时提出了创新的解决方案和未来的研究方向。我们的框架展示了多种基于免疫的方法的战略整合如何显著改善不同癌症类型的治疗结果,可能彻底改变癌症治疗范式。这种DDI的概念,通过合理的第三方药物选择得到加强,代表了解决肿瘤学迫切临床需求的一个有希望的方向。通过建立该方法的理论基础,我们旨在指导未来癌症免疫治疗的研究和临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
12.60
自引率
7.30%
发文量
97
审稿时长
6 weeks
期刊介绍: Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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