The Therapeutic Potential of Nanobodies

Abstract

Today, bio-medical efforts are entering the subcellular level, which is witnessed with the fast-developing fields of nanomedicine, nanodiagnostics and nanotherapy in conjunction with the implementation of nanoparticles for disease prevention, diagnosis, therapy and follow-up. Nanoparticles or nanocontainers offer advantages including high sensitivity, lower toxicity and improved safety-characteristics that are especially valued in the oncology field. Cancer cells develop and proliferate in complex microenvironments leading to heterogeneous diseases, often with a fatal outcome for the patient. Although antibody-based therapy is widely used in the clinical care of patients with solid tumours, its efficiency definitely needs improvement. Limitations of antibodies result mainly from their big size and poor penetration in solid tissues. Nanobodies are a novel and unique class of antigen-binding fragments, derived from naturally occurring heavy-chain-only antibodies present in the serum of camelids. Their superior properties such as small size, high stability, strong antigen-binding affinity, water solubility and natural origin make them suitable for development into next-generation biodrugs. Less than 30 years after the discovery of functional heavy-chain-only antibodies, the nanobody derivatives are already extensively used by the biotechnology research community. Moreover, a number of nanobodies are under clinical investigation for a wide spectrum of human diseases including inflammation, breast cancer, brain tumours, lung diseases and infectious diseases. Recently, caplacizumab, a bivalent nanobody, received approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with thrombotic thrombocytopenic purpura.

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

“…These molecular weights are similar to the fusion proteins studied, increasing the interest of the strategy proposed. Another approach is the nanobodies (smallest Ab-derivative) which reveal promising results in preclinical and clinical studies in the elimination of brain tumors [102,125,126].…”

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

“…HCAbs consist of only two heavy chains without light chains, thereby only containing a single variable domain (VHH) referred to as a single-domain antibody or Nb in the absence of the effector domain 12,13 . In addition to having affinities and specificities for antigens similar to those of traditional antibodies, Nbs show smaller size and higher stability than most antibodies 14,15 . Due to their structure nature, Nbs can be easily constructed into multivalent or multi-specific formats and produced with convenient steps of purification at low manufacturing cost 16,17 .…”

Development of Nanobodies as first-in-class inhibitors for the NEDP1 deNEDDylating enzyme

“…They can be easily expressed in cells as fusion proteins enabling the recognition of the target of interest in living cells. These features have already lead to a number of biotechnological and medical applications in which Nbs excel other antibody formats 30,31 .…”