Single domain Camelid antibody fragments for molecular imaging and therapy of cancer

Frontiers in Oncology

Oncology

Shulin Li¹  Sanne Johanna Maria Hoefnagel²  Kausilia Krishnawatie Krishnadath³ 

[1] Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands;Cancer Center Amsterdam, Amsterdam, Netherlands;Department of Clinical Geriatrics, Radboudumc, Nijmegen, Netherlands;Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium;Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium;

关键词: cancer;    VHHs;    mAbs;    imaging;    therapy;   

DOI  :  10.3389/fonc.2023.1257175

 received in 2023-07-12, accepted in 2023-08-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

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 18F and 99mTc 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.

【 授权许可】

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Copyright © 2023 Li, Hoefnagel and Krishnadath