Since the turn of the century, cancer therapy has undergone a transformation in terms of new treatment modalities and renewed optimism in achieving long-lived tumor control and even cure. This is, in large part, thanks to the widespread incorporation of monoclonal antibodies (mAbs) into standard treatment regimens. These new therapies have, across many settings, significantly contributed to improved clinical responses, patient quality of life and survival. Moreover, the flexibility of the antibody platform has led to the development of a wide range of innovative and combinatorial therapies that continue to augment the clinician’s armory. Despite these successes, there is a growing awareness that in many cases mAb therapy remains suboptimal, primarily due to inherent limitations imposed by the immune system’s own homeostatic controls and the immunosuppressive tumor microenvironment. Here, we discuss the principal barriers that act to constrain the tumor-killing activity of antibody-based therapeutics, particularly those involving antibody glycans, using illustrative examples from both pre-clinical and market approved mAbs. We also discuss strategies that have been, or are in development to overcome these obstacles. Finally, we outline how the growing understanding of the biological terrain in which mAbs function is shaping innovation and regulation in cancer therapeutics.

中文翻译：

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通过路障：克服有效的基于抗体的癌症治疗方法的障碍

自本世纪初以来，癌症治疗在实现长寿的肿瘤控制甚至治愈方面已经历了新的治疗方式和新的乐观主义的转变。这在很大程度上是由于将单克隆抗体（mAb）广泛纳入标准治疗方案中。在许多情况下，这些新疗法已为改善临床反应，患者的生活质量和生存做出了重大贡献。此外，抗体平台的灵活性已导致开发了广泛的创新和组合疗法，这些疗法继续增强了临床医生的能力。尽管取得了这些成功，但人们越来越意识到，在许多情况下，mAb疗法仍然不是最佳选择，主要是由于免疫系统自身的稳态控制和免疫抑制性肿瘤微环境所施加的固有限制。在这里，我们使用临床前和市场认可的单克隆抗体的示例性实例，讨论了主要的障碍，这些障碍可用来限制基于抗体的疗法（尤其是涉及抗体聚糖的疗法）的杀肿瘤活性。我们还将讨论已经或正在开发克服这些障碍的策略。最后，我们概述了对单克隆抗体在其中发挥作用的生物领域的日益了解如何塑造癌症疗法中的创新和调控。使用来自临床前和市场认可的单克隆抗体的说明性实例。我们还将讨论已经或正在开发克服这些障碍的策略。最后，我们概述了对单克隆抗体在其中发挥作用的生物领域的日益了解如何塑造癌症疗法中的创新和调控。使用来自临床前和市场认可的单克隆抗体的说明性实例。我们还将讨论已经或正在开发克服这些障碍的策略。最后，我们概述了对单克隆抗体在其中发挥作用的生物领域的日益了解如何塑造癌症疗法中的创新和调控。