Nuevos diseños nanobiotecnológicos frente a cáncer basados en inmunotoxinas

Abstract

Nowadays, the incidence and mortality of cancer remain one of the main risks to human health and lifespan, in spite of the development of biomedical technology and new diagnostic methods. Among the cancer classification, colorectal cancer remains in third place considering incidence, and second place considering mortality for global population. Current therapy consists of surgery, followed by chemotherapy or radiotherapy as adjuvant treatment. However, these are non-specific therapies, leading to systemic toxicity and affecting directly the quality of life of patients. That is why immunotherapy and the advent of monoclonal antibodies have arisen as a breakthrough in the treatment of this disease, as they are target therapies with great specificity and promising clinical results.Regarding passive immunotherapy based on monoclonal antibodies, immunotoxins are a type of immunoconjugates. Immunotoxins are chimeric molecules, with a target domain (usually an antibody or a derived from it) that targets specifically the action of a toxic domain (a toxic protein) towards the cancerous cell, leading to its death. Since immunotoxins were first conceived, they have undergone an evolution in its designs, with the use of smaller target domains, such as scFv (single chain fragment variable), VHH (nanobody) or trimeric formats (trimerbody) or using toxins from different sources, being less immunogenic. Regarding the latter, the use of fungal ribotoxins, being α-sarcin the most characterized member of fungal ribotoxins, has earned quite interest because of its high thermal stability, small size, low immunogenicity and high catalytic efficiency...