Monoclonal Antibodies
Development of a platform for the production of nanobodies (monoclonal shark antibodies).
Monoclonal Antibody-based
With the advent of monoclonal antibody-based biological therapy (mAb), the therapeutic possibilities are constantly expanding.
All of this goes hand in hand with the development of molecular biology, where it has created a greater understanding of the pathophysiology of disease. Antibody studies have generated and confirmed new targets that impact the pathogenesis of the disease, allowing personalized therapy.
The use of monoclonal antibodies directed against specific targets has made possible the development of a whole revolutionary universe of novel therapies. One of the newest technologies in antibody production is that of single domain nanobodies or nanoantibodies. Our proyect proposes the establishment of a platform for the production of nanobodies. These can be created on dromedaries or sharks.
The reason for using sharks for the production of antibodies is mainly due to the size of 12kDa which is 10 times smaller than human (150kd). The advantage of this size is that it gives them a greater chance of entering specific tissues such as the brain. Additionally, these nanobodies are highly resistant to heat and pH, and can retain their activity as they pass through the digestive tract.
Given their small size, these antibodies, after being selected, can be cloned and expressed in bacteria. While antibody therapies are revolutionizing medicine, this comes at a high cost. A treatment with human or humanized antibodies can carry a cost of several thousand dollars. On the other hand, if you could use nanobodies expressed in bacteria, the cost would be a couple of dollars per treatment. In addition to being able to be used in treatments, these antibodies could also be used in diagnosis.
Haematopoietic-Like Signalling
Molecular and functional characterization of haematopoietic-like signalling network in Glioblastoma.
Glioblastoma Multiforme
Glioblastoma multiforme (GBM) is one of the most aggressive human cancers characterized by diffuse infiltration of surrounding brain tissue and frequent resistance to adjuvant therapeutic modalities.
Current GBM therapy consists of surgical resection followed by radiation and temozolomide treatment1.
GBM patients remains
Despite intensive research, the median survival of GBM patients remains at 15-18 months, with less than 10% of patients surviving over 5 years, underlining the desperate need for novel therapeutic strategies.
Over 90 immune molecules (including T-cell receptors (TCR), B-cell receptors (BCR) and Fc receptors) have specific immunoreceptor tyrosine-based activation motifs (ITAMs) or ITAM-like motifs that play crucial roles in leukocyte function and signaling.
Following phosphorylation of the ITAM by a Src family member, these molecules signal mainly through SYK and ZAP705. ITAM-bearing viral proteins can act as oncogenes mediating neoplastic transformation not only of hematopoietic, but also non-hematopoietic cells including endothelia and epithelial cells.
Molecular profiling of GBM identified four distinct subtypes: neural, proneural, classical and mesenchymal8, although the proneural can spontaneously switch to mesenchymal. Even though the mesenchymal subgroup includes “immune genes”, this has been mainly assumed to reflect infiltrative cells, while earlier work on immune markers has been largely overlooked. We recently reported MerTK to be over expressed in GBM, where it promotes a glioma “stem” cell phenotype. MerTK is a well-characterized macrophage surface marker involved in the phagocytosis of apoptotic cells and has been identified within the mesenchymal GBM subtype.
Interestingly, single-cell analysis of GBM (which excluded CD45+cells) has found the mesenchymal signature in most samples with a high number of immunological molecules. Various studies have also reported that astrocytes and neural progenitor cells express MHC class II molecules as well as a range of hematopoietic receptors, such as CD86, CD80, CD90, CD3 and TCR-β. This suggests that the “immune” molecular signatures found in GBM may derive from tumor cells and could therefore play a pivotal role in gliomagenesis and progression.
Targeting Immune Kinase Inhibitors.
Kinases involved in autoimmune, inflammatory, and allergic diseases are seen as possible treatments for other diseases such as cancer.
Our project is based on using known compounds that have a non-specific inhibition against these kinases and identifying which modifications could have more potency and specificity.