Abstract
In the last decade, cancer immunotherapies have produced impressive therapeutic results. However, the potency of immunotherapy is tightly linked to immune cell infiltration within the tumor and varies from patient to patient. Thus, it is becoming increasingly important to monitor and modulate the tumor immune infiltrate for an efficient diagnosis and therapy. Various bispecific approaches are being developed to favor immune cell infiltration through specific tumor targeting. The discovery of antibodies devoid of light chains in camelids has spurred the development of single domain antibodies (also called VHH or nanobody), allowing for an increased diversity of multispecific and/or multivalent formats of relatively small sizes endowed with high tissue penetration. The small size of nanobodies is also an asset leading to high contrasts for non-invasive imaging. The approval of the first therapeutic nanobody directed against the von Willebrand factor for the treatment of acquired thrombotic thrombocypenic purpura (Caplacizumab, Ablynx), is expected to bolster the rise of these innovative molecules. In this review, we discuss the latest advances in the development of nanobodies and nanobody-derived molecules for use in cancer immunotherapy and immunoimaging.
Highlights
It is well established that tumor cells can interact with their environment to promote an immunosuppressive environment to favor their survival and proliferation
Following the success of immune checkpoint blockade therapies, different strategies based on the monoclonal success of antibodies immune checkpoint blockade therapies, different strategies based on monoclonal aiming at activating the T cell mediated anti-tumor response and overcome antibodies aiming at activating the cell anti-tumor response overcome immunotherapy immunotherapy resistance are currentlymediated under intense investigation
The antigen binding domain (ABD) binds HER2 positive tumor cells, thereby recruiting dinitrophenol group (DNP)-specific IgG1 serum antibodies, which trigger NK cells through FcγRIII, resulting in tumor cell killing by antibody dependent cell-mediated cytotoxicity (ADCC)
Summary
It is well established that tumor cells can interact with their environment to promote an immunosuppressive environment to favor their survival and proliferation. Combination therapies are emerging as the path to increase response rates and tackle cancer cell escape mechanisms [4] Their success often relies on the presence of immune cell within the tumor and their interaction with immunosuppressive ligands expressed by tumor cells. Nanobodies are characterized by a good solubility and stability to pH and temperatures Their small size allows for a better penetration within tissue and in cell–cell interfaces like immune synapses [13]. Nanobodies can be used to engineer larger molecules with several valencies or specificities and can be conjugated to imaging agent or drug delivery systems Their high modularity increases further the format possibilities to crease small size antibody-derived molecules for therapy and imaging (Figure 1). Nb: nanobody; ARD: antigen recognition domain; TAA: tumor molecules discussed in this review. TAA: Tumor associated antigen; antigen; IC: Immune checkpoint; ARD: Antibody recruiting domain.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
