Download Nanomedicine Seminars 2015_1

Nanomedicine Seminars 2015
Organizers: University of Trieste & University of Nova Gorica (Tatiana Da Ros, Lucia Pasquato, Ario de Marco)
Location: University of Trieste, room 207, second floor building C11
April - Tuesday 21st
14:00 Introduction
14:15 Ario de Marco (University of Nova Gorica)
“RESEARCH AND CLINICAL OPPORTUNITIES OFFERED BY RECOMBINANT ANTIBODIES”
15:15 Barbara Molon (University of Padova)
“IMPROVING CANCER IMMUNOTHERAPY BY PREVENTING CHEMOKINE NITRATION”
16:15 Rita Musetti (University of Udine)
“IMMUNOELECTRON MICROSCOPY: A RELIABLE TOOL FOR THE ANALYSIS OF CELL PROCESSES”
Abstracts:
“RESEARCH AND CLINICAL OPPORTUNITIES OFFERED BY RECOMBINANT ANTIBODIES”
Conventional antibodies (IgG molecules) are essential in basic research and in vitro diagnostics because of their
excellent binding specificity. However, their large mass (150 kDa) and scarce suitability for engineering impair
their effective exploitation in several in vivo applications. IgG fragments have been proposed to obtain smaller
molecules that preserve the same binding specificity for their antigen but possess improved tissue penetration.
Recombinant antibodies –and specifically single-domain antibodies (nanobodies/VHHs)- know an exponentially
growing interest in biotechnology because they minimize the mass (15 kDa), reduce the immunogenicity, and
simplify the engineering into application-adapted reagents. Furthermore, the first VHHs have successfully
completed the clinical phase II, the patents which protected the technology have expired, and their
biochemical/biophysical features are particularly favorable (extremely stable, easy to produce and modify, with
affinity and avidity that can be tuned according to the needs).
Nanobodies are not simply another antibody form to use for standard immunological assays. They are
extremely precious binders that can be easily fused to tags, drugs, macromolecules, are used for the
functionalization of substrates, nanoparticles, sensors, and are produced cost-effectively as reliable reagents
for a variety of biotechnological applications.
“IMPROVING CANCER IMMUNOTHERAPY BY PREVENTING CHEMOKINE NITRATION”
The goal of all immunotherapeutic approaches against solid tumors is the induction and expansion of tumor
infiltrating T lymphocytes (TILs) that invade tumor mass and kill transformed cells. Typically, TILs are unable to
reach the core of the tumor mass, and they concentrate at the border of the neoplastic lesion. Several barriers
can limit complete trafficking and migration of lymphocytes within cancerous tissues. We speculated that
reactive nitrogen species (RNS) could affect chemokine biology and contribute to keep TILs distant from the
tumor core. Chemokines are small cytokines with selective chemoattractant properties, coordinating the
homeostatic circulation of leukocytes as well as their movement to sites of inflammation or injury. Deregulated
expression of chemokines and their receptors is a signature of many human diseases, including autoimmunity
and chronic inflammation, as well as immunodeficiency and cancer. We found that the chemoattractants
CXCL12, CCL21, and CCL2 lost their ability to recruit T lymphocytes when exposed to peroxynitrite, RNS present
in tumor microenviroment. However, the modified CCL2 chemokine retains its capacity of recruiting myeloid
cells. These data suggest that RNS-altered chemokines may modify the tumor microenvironment and favor
immune escape. Based on our findings, drugs controlling the in situ production of RNS might be useful to aid
immunotherapeutic approaches for the treatment of cancer, by creating a favorable tumor environment for
lymphocyte recruitment and activation. Using in vitro screenings, we have developed novel small molecules
aimed at interfering with multiple, interconnected metabolic pathways leading to RNS generation in the tumor
microenvironment. Pre-conditioning of the tumor microenvironment with novel drugs that inhibit RNS
production facilitates CTL invasion of the tumor and promotes an effective cancer immunotherapy.
“IMMUNOELECTRON MICROSCOPY: A RELIABLE TOOL FOR THE ANALYSIS OF CELL PROCESSES”
Electron Microscopy is an indispensable tool to investigate the structures of the cell and organelles, and also to
study the cellular biological processes implicated in the responses to environmental changes.
Among the different techniques availble in electron microscopy, immunoelectron microscopy emerges as a tool
linking biochemistry, molecular biology and ultrastructural studies. Immunoelectron microscopy provides
informations about the localization of proteins in cells and tissues, connecting a visible cell structure with a
specific in situ localization of molecules at high resolution, so providing insights into the structure-function
associations.