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5.2.3 Study of the Biomarkers in Blood
Samples
The proteins identified in the PBZ are components
of the brain cells exosomes, and thus can be assayed
in blood samples from patients.
We look forward to this possibility because
blood samples are easy to obtain and allow repetitive
and reproductive measure of biomarkers blood level
in GB patients during their post-surgical evolution
and treatment.
We will assess the presence of these biomarkers
in the peripheral blood of GB patients using an
enzyme-linked immuno-assay (ELISA) technique.
As with the analysis of the tumor samples, a
preliminary study will be performed on a small
cohort of patients from the clinico-biological
collection and will be extended to the whole cohort
if the first results are positives.
5.2.4 Biomarkers as Therapeutic Targets
We will study the potential role of the identified
biomarkers as therapeutic target in GB treatment. A
step next will be to develop monoclonal antibodies
targeted against these proteins to see if the specific
neutralization of one of these proteins can improve
the survival or the therapeutic response of a
population of murine GB model.
If we identify a significant improvement in terms
of survival after GB implantation in a murine model
of the disease, we will begin a human clinical trial.
5.2.5 Biomarkers as Targets for Vectorized
Therapies
One other axis of development will be the use of
vectorized LNC aimed against the proteins identified
in the GB-PBZ. Production of LNC, encapsulation
of chemotherapeutic agents and targeted delivery of
these nanocapsules are a field of expertise of my
laboratory, which possess an international
recognition in this domain.
We aim to produce LNC targeted against the
identified biomarkers to use them as therapeutic
agent against GB. In a first phase, we will produce
LNC containing fluorochromes to assess the
distribution of the LNC in a murine model of GB.
Then, if the results are positive, we will produce
LNC containing a chemotherapeutic agent, and
assess in the same murine model of GB the impact
of the LNC injection in the functional prognosis and
survival of the mice, with always as first aim the
transfer of these researches to the clinical field in
human.
6 EXPECTED OUTCOME
At short-term, during the next year, the results of the
SHIM and TPEF imaging analysis of brain tumor
samples will be the subject of a publication in a high
impact review of Neuro-Oncology. Also the
validation of the biomarkers in the brain tumor and
the peripheral blood samples of the patients will be
the subject of a publication in a high impact review
in Neuro-Oncology.
The use of per-operative OCT or colorimetric
staining of the tumor are planned for the end of my
PhD thesis or will be the subject of my post-doctoral
studies.
The use of the proteins of interest as therapeutic
target or as target for chemotherapy-loaded LNC
will be the subject of further studies in my
laboratory, implicating Pharmacists and Galenists.
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