Li Shulin, Hoefnagel Sanne Johanna Maria, Krishnadath Kausilia Krishnawatie
Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands.
Cancer Center Amsterdam, Amsterdam, Netherlands.
Front Oncol. 2023 Sep 8;13:1257175. doi: 10.3389/fonc.2023.1257175. eCollection 2023.
Despite innovations in cancer therapeutics, cancer remains associated with high mortality and is one of biggest health challenges worldwide. Therefore, developing precise cancer imaging and effective treatments is an unmet clinical need. A relatively novel type of therapeutics are heavy chain variable domain antibody fragments (VHHs) derived from llamas. Here, we explored the suitability of VHHs for cancer imaging and therapy through reviewing the existing literature. We searched the MEDLINE, EMBASE and Cochrane databases and identified 32 papers on molecular imaging and 41 papers on therapy that were suitable for comprehensive reviewing. We found that VHHs harbor a higher specificity and affinity compared to mAbs, which contributes to high-quality imaging and less side-effects on healthy cells. The employment of VHHs in cancer imaging showed remarkably shorter times between administration and imaging. Studies showed that F and Tc are two optimal radionuclides for imaging with VHHs and that site-specific labelling is the optimal conjugation modality for VHHs with radionuclide or fluorescent molecules. We found different solutions for reducing kidney retention and immunogenicity of VHHs. VHHs as anticancer therapeutics have been tested in photodynamic therapy, targeted radionuclide therapy, immunotherapy and molecular targeted therapy. These studies showed that VHHs target unique antigen epitopes, which are distinct from the ones recognized by mAbs. This advantage means that VHHs may be more effective for targeted anticancer therapy and can be combined with mAbs. We found that high cellular internalization and specificity of VHHs contributes to the effectiveness and safety of VHHs as anticancer therapeutics. Two clinical trials have confirmed that VHHs are effective and safe for cancer imaging and therapy. Together, VHHs seem to harbor several advantages compared to mAbs and show potential for application in personalized treatment for cancer patients. VHH-based imaging and therapy are promising options for improving outcomes of cancer patients.
尽管癌症治疗方法有所创新，但癌症仍然与高死亡率相关，是全球最大的健康挑战之一。因此，开发精确的癌症成像技术和有效的治疗方法是尚未满足的临床需求。一种相对新颖的治疗方法是源自骆驼的重链可变区抗体片段（VHHs）。在此，我们通过回顾现有文献探讨了VHHs在癌症成像和治疗中的适用性。我们检索了MEDLINE、EMBASE和Cochrane数据库，确定了32篇关于分子成像的论文和41篇关于治疗的论文，适合进行全面综述。我们发现，与单克隆抗体相比，VHHs具有更高的特异性和亲和力，这有助于高质量成像，并对健康细胞产生较少的副作用。VHHs在癌症成像中的应用显示，给药与成像之间的时间显著缩短。研究表明，氟和锝是与VHHs成像的两种最佳放射性核素，位点特异性标记是VHHs与放射性核素或荧光分子结合的最佳方式。我们找到了减少VHHs肾脏滞留和免疫原性的不同解决方案。VHHs作为抗癌治疗药物已在光动力疗法、靶向放射性核素疗法、免疫疗法和分子靶向疗法中进行了测试。这些研究表明，VHHs靶向独特的抗原表位，这些表位与单克隆抗体识别的表位不同。这一优势意味着VHHs可能对靶向抗癌治疗更有效，并且可以与单克隆抗体联合使用。我们发现VHHs的高细胞内化和特异性有助于其作为抗癌治疗药物的有效性和安全性。两项临床试验已证实，VHHs在癌症成像和治疗中是有效且安全的。总体而言，与单克隆抗体相比，VHHs似乎具有几个优势，并显示出在癌症患者个性化治疗中的应用潜力。基于VHHs的成像和治疗是改善癌症患者治疗效果的有前景的选择。
