Nanobodies, also known as VHH domains, are the smallest known natural antigen-binding fragments derived from heavy-chain-only antibodies of camelids. Their unique characteristics such as high stability, solubility, specificity, and ease of genetic manipulation have led to their fusion with other proteins creating an array of nanobody-based fusion proteins for therapeutic and diagnostic purposes. This article will delve into different types of these fusion proteins and their applications.
One of the most promising applications of nanobody-based fusion proteins is in cancer immunotherapy. For instance, nanobodies specific for tumor antigens have been fused to immune effector proteins like cytokines or immune-checkpoint inhibitors, creating powerful tools for targeted cancer therapy. For example, a humanized nanobody/IgG1-Fc fusion protein has shown promising therapeutic potential in preclinical models of cancer. By targeting specific cancer cell antigens, these fusion proteins can direct the body's immune response specifically towards cancer cells, reducing damage to healthy tissues.
Nanobody-based fusion proteins have also found applications in diagnostics. By fusing nanobodies to fluorescent proteins or enzyme reporters, scientists can create biosensors that detect specific antigens. For instance, a fusion protein of anti-GFP nanobody and a fluorescent protein can specifically label GFP fusion proteins in cellular studies, aiding in the visualization of protein localization and dynamics in real-time. Similarly, nanobody-horseradish peroxidase fusion proteins have been used as ultrasensitive probes in immunoassays.
The small size and high stability of nanobodies make them ideal for targeted drug delivery. By fusing nanobodies to therapeutic agents or drug-loaded nanoparticles, researchers can develop systems that deliver drugs directly to specific cells or tissues. For example, a nanobody-based carrier platform has been developed for targeting inside blood vessels, allowing for precise intravascular diagnostics and therapies for cardiovascular diseases.
Nanobodies can also be fused with radioactive isotopes to create radiotracers for imaging in nuclear medicine. These nanobody-based radiotracers can be used for both diagnostic imaging and targeted radionuclide therapy, particularly in the context of cancer. For instance, radiolabeled nanobodies targeting HER2, a protein overexpressed in some breast cancers, have been used for both imaging of the tumor and targeted therapy.