RESUMEN
Vγ9Vδ2-T cells constitute the predominant subset of γδ-T cells in human peripheral blood and have been shown to play an important role in antimicrobial and antitumor immune responses. Several efforts have been initiated to exploit these cells for cancer immunotherapy, e.g. by using phosphoantigens, adoptive cell transfer, and by a bispecific monoclonal antibody based approach. Here, we report the generation of a novel set of Vγ9Vδ2-T cell specific VHH (or nanobody). VHH have several advantages compared to conventional antibodies related to their small size, stability, ease of generating multispecific molecules and low immunogenicity. With high specificity and affinity, the anti-Vγ9Vδ2-T cell receptor VHHs are shown to be useful for FACS, MACS and immunocytochemistry. In addition, some VHH were found to specifically activate Vγ9Vδ2-T cells. Besides being of possible immunotherapeutic value, these single domain antibodies will be of great value in the further study of this important immune effector cell subset.
Asunto(s)
Afinidad de Anticuerpos/inmunología , Especificidad de Anticuerpos/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Anticuerpos de Dominio Único/inmunología , Linfocitos T/inmunología , Animales , Camélidos del Nuevo Mundo/inmunología , Células Cultivadas , Citometría de Flujo/métodos , Humanos , Inmunohistoquímica/métodos , Separación Inmunomagnética/métodos , Células Jurkat , Microscopía Fluorescente , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Reproducibilidad de los Resultados , Linfocitos T/metabolismoRESUMEN
Over the past decades advances in bioengineering and expanded insight in tumor immunology have resulted in the emergence of novel bispecific antibody (bsAb) constructs that are capable of redirecting immune effector cells to the tumor microenvironment. (Pre-) clinical studies of various bsAb constructs have shown impressive results in terms of immune effector cell retargeting, target dependent activation and the induction of anti-tumor responses. This review summarizes recent advances in the field of bsAb-therapy and limitations that were encountered. Furthermore, we will discuss potential future developments that can be expected to take the bsAb approach successfully forward.
Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias/terapia , Animales , Anticuerpos Biespecíficos/farmacología , Antineoplásicos/farmacología , Evaluación Preclínica de Medicamentos , Humanos , Inmunoterapia , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Terapia Molecular Dirigida , Neoplasias/inmunología , Anticuerpos de Cadena Única/farmacología , Anticuerpos de Cadena Única/uso terapéuticoRESUMEN
Over the years, many antibodies have been successfully generated to treat patients with life-threatening diseases, most notably cancer. While the first generation of antibodies, originating from mice, caused severe side effects and were relatively inefficient, technological advances have made it possible to obtain fully human antibodies for therapeutic use. 'Heavy-chain only' antibodies have recently been discovered in the blood of camelids. Because of their size, the antigen-binding units of these antibodies comprising only a single Ig fold are called Nanobodies. These antibody fragments have several remarkable features that make them ideal candidates as next-generation cancer therapeutics. Particularly appealing is their ability to simultaneously inhibit various crucial growth factor receptors or their ligands with a single molecule. In addition, they are easy to clone and express on the tip of filamentous phage, which opens the possibility to select for Nanobodies inducing particular biological effects. Nanobodies have potential to become important cancer therapeutics in the near future, displaying unequalled and unprecedented efficacies in treatment.