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Updated: Jul 15, 2025
In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research
Published on: September 16, 2019
Single domain Camelid antibody fragments for molecular imaging and therapy of cancer
Shulin Li1,2, Sanne Johanna Maria Hoefnagel3, Kausilia Krishnawatie Krishnadath4,5
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands.
Abstract:
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.
Insights
Heavy chain variable domain antibody fragments (VHHs) derived from llamas show promise for cancer imaging and therapy. VHHs offer higher specificity and efficacy than traditional antibodies, with clinical trials confirming their safety and effectiveness.
Area of Science:
- Biomedical sciences
- Immunology
- Oncology
Background:
- Cancer poses a significant global health challenge, necessitating advancements in precise imaging and effective treatments.
- Heavy chain variable domain antibody fragments (VHHs), derived from llamas, represent a novel class of therapeutic and imaging agents.
- Current therapeutic strategies require improvement for enhanced specificity and reduced side effects.
Purpose of the Study:
- To review the existing literature on the application of VHHs in cancer imaging and therapy.
- To evaluate the suitability of VHHs as alternatives to conventional monoclonal antibodies (mAbs).
- To identify advantages and potential challenges of VHHs in oncology.
Main Methods:
- Comprehensive literature search of MEDLINE, EMBASE, and Cochrane databases.
- Identification and review of 32 papers on VHHs in molecular imaging and 41 papers on VHHs in cancer therapy.
- Analysis of VHH characteristics, including specificity, affinity, imaging parameters, therapeutic applications, and clinical trial outcomes.
Main Results:
- VHHs exhibit higher specificity and affinity than mAbs, leading to improved imaging quality and reduced side effects.
- VHH-based imaging demonstrates shorter administration-to-imaging times, with 18F and 99mTc identified as optimal radionuclides.
- Site-specific labeling is optimal for VHH conjugation, and strategies exist to mitigate kidney retention and immunogenicity.
- VHHs show efficacy in various therapeutic modalities, targeting distinct epitopes and offering potential combination therapy with mAbs.
- High cellular internalization and specificity contribute to VHH effectiveness and safety, supported by two positive clinical trials.
Conclusions:
- VHHs present significant advantages over mAbs for cancer imaging and therapy.
- Their high specificity, efficacy, and safety profile suggest potential for personalized cancer treatment.
- VHH-based approaches are promising for improving patient outcomes in oncology.
