Nanobody Engineering and strategies targeting the immune stroma of tumors.

You are here:
< All Topics

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.

Figure 1. Nanobody-based formats in development for tumor immunotherapy and imaging.
(A) Camelids specificity domains derived of conventional IgG1 or HcAbs (IgG2 and IgG3).
The nanobody crystal structure shown is pdb entry 6GZP. (B) Formats of nanobody engineered
molecules discussed in this review. Nb: nanobody; ARD: antigen recognition domain; TAA: tumor
associated antigen.
Figure 2. Nanobody-based strategies targeting the immune stroma of tumors. Nanobody-derived
immunomodulatory molecules are under investigation to increase anti-tumor immunity (orange
arrows) and prevent tumor-driven immune suppression (blue arrows). TAA: Tumor associated antigen;
IC: Immune checkpoint; ARD: Antibody recruiting domain.

Ref: Nanobody Engineering: Toward Next Generation Immunotherapies and Immunoimaging of Cancer. Antibodies (Basel). 2019 Jan 21;8(1):13. doi: 10.3390/antib8010013.

Table of Contents