前沿:单克隆抗体在实体瘤治疗中的肿瘤内递送。

Leading Edge: Intratumor Delivery of Monoclonal Antibodies for the Treatment of Solid Tumors.

机构信息

Oncoimmunology Unit, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), 31008 Pamplona, Spain.

Division of Gene Therapy and Regulation of Gene Expression, Instituto de Investigación Sanitaria de Navarra (IdISNA), Cima Universidad de Navarra, 31008 Pamplona, Spain.

出版信息

Int J Mol Sci. 2023 Jan 31;24(3):2676. doi: 10.3390/ijms24032676.

Abstract

Immunotherapies based on immune checkpoint blockade have shown remarkable clinical outcomes and durable responses in patients with many tumor types. Nevertheless, these therapies lack efficacy in most cancer patients, even causing severe adverse events in a small subset of patients, such as inflammatory disorders and hyper-progressive disease. To diminish the risk of developing serious toxicities, intratumor delivery of monoclonal antibodies could be a solution. Encouraging results have been shown in both preclinical and clinical studies. Thus, intratumor immunotherapy as a new strategy may retain efficacy while increasing safety. This approach is still an exploratory frontier in cancer research and opens up new possibilities for next-generation personalized medicine. Local intratumor delivery can be achieved through many means, but an attractive approach is the use of gene therapy vectors expressing mAbs inside the tumor mass. Here, we summarize basic, translational, and clinical results of intratumor mAb delivery, together with descriptions of non-viral and viral strategies for mAb delivery in preclinical and clinical development. Currently, this is an expanding research subject that will surely play a key role in the future of oncology.

摘要

基于免疫检查点阻断的免疫疗法在许多肿瘤类型的患者中显示出显著的临床疗效和持久的反应。然而,这些疗法在大多数癌症患者中缺乏疗效,甚至在一小部分患者中引起严重的不良反应,如炎症性疾病和超进展性疾病。为了降低发生严重毒性的风险,肿瘤内递送单克隆抗体可能是一种解决方案。在临床前和临床研究中都取得了令人鼓舞的结果。因此,肿瘤内免疫疗法作为一种新策略可能在保持疗效的同时提高安全性。这种方法仍然是癌症研究中的一个探索性前沿领域,为下一代个体化医学开辟了新的可能性。肿瘤内的单克隆抗体递送可以通过多种方式实现,但一种有吸引力的方法是使用在肿瘤内表达 mAb 的基因治疗载体。在这里,我们总结了肿瘤内 mAb 递送的基础、转化和临床结果,以及非病毒和病毒策略在临床前和临床开发中用于 mAb 递送的描述。目前,这是一个正在不断发展的研究课题,它肯定将在肿瘤学的未来中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51b2/9917067/62b1ec7f3c6a/ijms-24-02676-g001.jpg

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