Department of Sciences and Technologies, University of Sannio, Via Francesco de Sanctis, 82100 Benevento, Italy.
Int J Mol Sci. 2022 Oct 18;23(20):12499. doi: 10.3390/ijms232012499.
Biological therapy, with its multifaceted applications, has revolutionized the treatment of tumors, mainly due to its ability to exclusively target cancer cells and reduce the adverse effects on normal tissues. This review focuses on the therapies targeting the CXCR4 and CD47 receptors. We surveyed the results of early clinical trials testing compounds classified as nonpeptides, small peptides, CXCR4 antagonists or specific antibodies whose activity reduces or completely blocks the intracellular signaling pathways and cell proliferation. We then examined antibodies and fusion proteins against CD47, the receptor that acts as a "do not eat me" signal to phagocytes escaping immune surveillance. Despite these molecules being tested in early clinical trials, some drawbacks are emerging that impair their use in practice. Finally, we examined the ImmunoGenic Surrender mechanism that involves crosstalk and co-internalization of CXCR4 and CD47 upon engagement of CXCR4 by ligands or other molecules. The favorable effect of such compounds is dual as CD47 surface reduction impact on the immune response adds to the block of CXCR4 proliferative potential. These results suggest that a combination of different therapeutic approaches has more beneficial effects on patients' survival and may pave the way for new accomplishments in personalized anticancer therapy.
生物疗法具有多方面的应用，彻底改变了肿瘤的治疗方式，主要是因为其能够专门针对癌细胞，并减少对正常组织的不良反应。本综述重点介绍了针对 CXCR4 和 CD47 受体的治疗方法。我们调查了早期临床试验的结果，这些试验测试了被归类为非肽、小肽、CXCR4 拮抗剂或特异性抗体的化合物，这些化合物的活性降低或完全阻断了细胞内信号通路和细胞增殖。然后，我们研究了针对 CD47 的抗体和融合蛋白，CD47 是一种“不要吃我”的信号受体，可使逃避免疫监视的吞噬细胞失活。尽管这些分子在早期临床试验中进行了测试，但出现了一些缺陷，影响了它们在实践中的应用。最后，我们研究了免疫原性投降机制，该机制涉及 CXCR4 和 CD47 在配体或其他分子与 CXCR4 结合时的串扰和共内化。这种化合物的有利效果是双重的，因为 CD47 表面减少对免疫反应的影响增加了对 CXCR4 增殖潜力的阻断。这些结果表明，不同治疗方法的组合对患者的生存有更有益的影响，并可能为个性化抗癌治疗的新成就铺平道路。
