BIOTHERAPEUTICS AND BIOCOMPATIBLE DRUG DELIVERY SYSTEMS

The "Biotherapeutics and biocompatible drug delivery systems " course is one of the training activities of the PhD course in Bio and Nanomaterials Science and Technology and is divided in two modules: "Biotherapeutics" (module A) and "Biocompatible drug delivery systems" (module B). The module A allows students to acquire the knowledge of the main concepts related to the properties, the development and the applications of the major biomacromolecules and cell-based therapies. The module B allows students to acquire the knowledge on the development of materials and techniques in the frame of chemico-physico-biological analyses useful for the development of bio- and nanotechnologies.

The aim of module A ("Biotherapeutics") is to introduce the students to biotherapeutics, engineered biomacromolecules and cells that are developed by means of biological processes involving recombinant technologies. Particular attention will be dedicated to the properties and the methodologies used to develop most of the biomacromolecules (e.g. nucleic acids, peptides and proteins) and cells (e.g. immune cells, stem cells, red blood cells) currently used in the clinic. The students are supposed to be able to appreciate the advantages and the disadvantages of the different biotherapeutics and being able to recognise and evaluate, through a critical analysis, which molecular format may be more suitable for a given therapeutic application.
The aim of module B ("Biocompatible drug delivery systems") is to provide the students with the knowledge on the applications of bionanomaterials to cancer therapy. The students are guided in the understanding of the actual strategies to deliver chemo- and targeted-therapies in cancer patients by mean of nanomaterials. Analysing the history of chemo- and target-therapies together with drug delivery, the students acquire the rationale of the key steps pursued by scientists to overcome actual biological barriers and the misunderstanding and pitfalls that are still there.

Basic knowledge of nanomaterials, pharmacology, molecular, chemical, structural and cellular biology.

Contents of module A include:
• Peptide therapeutics: advantages and disadvantages. Natural product derived peptides as starting points for drug discovery. Display technologies in peptide lead discovery: phage display, mRNA display and ribosome display. Stapled peptides. Strategies to extend the half-life of peptides;
• Cytokine-based therapies: benefits and limitations. Interleukins approved for therapy. Engineering and synthetic cytokines signalling for therapeutics.
• Non-antibody scaffold drugs: advantages and major challenges. Strategies for the generation of differentiated non-antibody scaffold drugs. Examples of non-antibody scaffold molecules for therapeutic, diagnostic and biotechnological applications.
• Therapeutic antibodies: properties and mode of actions. Multidimensional engineering of antibodies: antigen binding, Fc receptor binding and modularity. Multispecific antibodies. Antibody fragments. Antibody drug conjugates (ADCs).
• Cell-based therapies. Adoptive cell therapy using tumour-infiltrating lymphocytes (TIL). Engineered T cell expressing chimeric antigen receptors (CAR-T). Therapeutic approaches to enhance natural killer (NK) cell cytotoxicity against cancer. Macrophages in immunotherapy. Engineering stem cells for cancer therapy. Dendritic cell (DC) in cancer immunotherapy. Antigen-specific therapeutic approaches for autoimmunity. Red blood cell-based therapies.
• Nucleic acid therapeutics: advantages and disadvantages. Principle of systematic evolution of ligands by exponential enrichment (SELEX). DNA, RNA aptamers. Antisense oligonucleotide (AON). RNA interference (RNAi). Ribozymes.

Contents of module B include:
• Chemotherapy - a historical overview with examples focused on the development and application of nitrogen mustard, folic acid, vinca alkaloids, taxanes and cisplatin.
• Target therapies - the development and application of imatinib, gefitinib and bevacizumab.
• Hallmarks of cancers - an analysis of the principles which govern cancer complexity: sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism and evading immune destruction.
• Barriers in drug delivery - principles of nanomedicine and the biological barriers: passive against active targeting, the mononuclear phagocyte system, nonspecific distribution of nanoparticles, hemorheological limitations, intratumoral pressure, cell membrane internalization, endosomal escape and multi drug resistance mechanisms.
• Misunderstandings and pitfalls - common mistakes and underestimations in nanoparticle testing: nanoparticles extravasation, tissue penetration and formulation; difference between mouse models and human; approaches to metastatic cancer; personalized therapy.
• Doxil, a history of success - rational for the development of a liposomal drug: slow drug release, site avoidance, accumulation in the tumor, protein binding, RES clearance, glomerular filtration, microvasculature permeability, extravascular transport; stealth technology and remote loading; applications in clinic.
• CRISPR/CAS9 technology – a historical overview; bacterial CRISPR-CAS systems; CRISPR technology in human; Applications and limitations in cancer.

All needed material will be provided in class.

The assessment of learning takes place by means of a short oral presentation. The objective of the exam consists in verifying and evaluating the ability of the student to include at least one content of the course in her/his current PhD research project. The students must demonstrate a critical thinking and the ability to expose the topic in a formal and concise manner using an appropriate scientific language. The constant and active participation to the lessons will be taken into account in the final evaluation.

Teaching is organized in frontal theoretical lectures in the classroom. PowerPoint slides will be used during the lessons. The teaching material is present and downloadable from the University's Moodle e-learning platform.

English

Teaching language: English

oral

This subject deals with topics related to the macro-area "Human capital, health, education" and contributes to the achievement of one or more goals of U. N. Agenda for Sustainable Development