Desarrollo de anticuerpos bi-específicos de unión a células NK (BiKE) frente al antígeno Tn para inmunoterapia en cáncer

Paúl Bernal, Jorge
Pardo Jimeno, Julián (dir.) ; Hurtado Guerrero, Ramón (dir.)

Universidad de Zaragoza, CIEN, 2023

Máster en Biología Molecular y Celular

Resumen: Introduction and objective. BiKEs (bispecific killer cell engagers) are a new form of immunotherapy that consists of two connected scFv. One scFv recognizes a tumor antigen and the other binds to CD16 on the NK cell membrane, thus NK cells are activated and specifically target the tumor. It’s thought that BiKEs would have the advantage over monoclonal antibodies of more easily penetrating solid tumors and generating a stronger stimulus to NK cells that would be capable of activating them even in the immunosuppressive conditions of the tumor microenvironment. The objective of this work is to design and recombinantly express two BiKEs, in addition to three other proteins, using the Tn antigen as a target. This antigen is an aberrant glycosylation pattern specific to tumor cells and highly abundant in tumors of epithelial origin.
Results. The 5 proteins have been expressed in HEK 293 6F cells with a good yield and degree of purity. We have been able to demonstrate that these proteins are correctly folded, dimerized and glycosylated. We also have probed that the scFvs of the BiKEs recognize Tn antigen as is described in the literature. However, the ability of BiKEs to activate NK cells against tumor cells in in vitro cultures couldn’t be demonstrated due to the lack of an adequate positive control.

Tipo de Trabajo Académico: Trabajo Fin de Master