Department of Pharmaceutical Science, University at Buffalo, Buffalo, NY 14214, USA.
Cancer Biol Med. 2021 Aug 15;18(3):649-64. doi: 10.20892/j.issn.2095-3941.2020.0704.
Despite the significant resources dedicated to the development of monoclonal antibody (mAb) therapies for solid tumors, the clinical success, thus far, has been modest. Limited efficacy of mAb in solid tumors likely relates to unique aspects of tumor physiology. Solid tumors have an aberrant vasculature and a dense extracellular matrix that slow both the convective and diffusive transport of mAbs into and within tumors. For mAbs that are directed against cellular antigens, high antigen expression and rapid antigen turnover can result in perivascular cells binding to and eliminating a significant amount of extravasated mAb, limiting mAb distribution to portions of the tumor that are distant from functional vessels. Many preclinical investigations have reported strategies to improve mAb uptake and distribution; however, to our knowledge, none have translated into the clinic. Here, we provide an overview of several barriers in solid tumors that limit mAb uptake and distribution and discuss approaches that have been utilized to overcome these barriers in preclinical studies.
尽管为开发用于实体瘤的单克隆抗体 (mAb) 疗法投入了大量资源，但迄今为止，临床疗效仍较为有限。mAb 在实体瘤中的疗效有限可能与肿瘤生理学的独特方面有关。实体瘤具有异常的脉管系统和密集的细胞外基质，这会减缓 mAb 向肿瘤内和肿瘤内的对流和扩散运输。对于针对细胞抗原的 mAb，高抗原表达和快速抗原周转会导致血管周围细胞结合并消除大量外渗的 mAb，从而将 mAb 分布限制在远离功能血管的肿瘤部分。许多临床前研究报告了改善 mAb 摄取和分布的策略；但是，据我们所知，这些策略都没有转化为临床实践。在这里，我们概述了实体瘤中限制 mAb 摄取和分布的几个障碍，并讨论了在临床前研究中用于克服这些障碍的方法。
