91042 - Molecular Pharmacology and Pharmacotherapy of Biotechnological Drugs

Learning outcomes

At the end of the module the student: - knows the structure, production and post-translational processes of recombinant proteins, purification processes and therapeutic targets of biotechnological drugs on the market; - knows the different classes of therapeutic proteins and monoclonal antibodies and their pharmacodynamic and pharmacokinetic profile; - knows the profile of activity, immunogenicity and safety of biotechnological drugs and biosimilars; - knows how to apply the knowledge learned for the conduct of the profession, for the proper conservation and dispensation of biotechnological drugs and to inform and educate patients in their use and monitor the management of appropriateness in their use and the continuity of adherence to drug therapy in chronic therapies.

Course contents

MODULE 1

GENETIC ENGINEERING AND RECOMBINANT DNA
Gene cloning. Cellular genetic engineering for drug-protein production. Methods of DNA transfer in cultured cells. Cell systems for the study and production of recombinant proteins. Cloning of a human gene. Post-translational modifications of proteins. Pharmacological applications of recombinant cell lines. Transgenic animals in drug research, development and production
MONOCLONAL ANTIBODIES
Structure of antibodies. Activity and recycling of antibodies. Biotechnological synthesis of antibodies. Growth and selection of hybridomas. Chimeric, humanized and fully human monoclonal antibodies. Modifications that improve the pharmacological properties of monoclonal antibodies. Small molecule conjugated antibodies

OLIGONUCLEOTIDES AS DRUGS
Classification of oligonucleotides. Mechanism of action of oligonucleotides.

PHARMACODYNAMICS

Mechanisms of action of monoclonal antibodies. Antibodies directed to tumor antigens. Modification of the organism's response. Mechanisms of action in non-anticancer therapies. Monoclonal antibodies conjugated with cytotoxic agents. Selectivity of action. Side effects of monoclonal antibodies.

PHARMACOKINETICS
Routes of administration of biotechnological drugs. ADME. Salvage pathway. Properties of the antigen. Immunogenicity

CLINICAL USE OF BIOTECHNOLOGICAL DRUGS

DRUGS FOR THE CARDIOVASCULAR SYSTEM
Dyslipidemias: cardiovascular risk factors. Monoclonal antibodies for the treatment of dyslipidemias. Fibrinolytic drugs. New potential therapeutic targets

Diseases of the bone and calcium metabolism.

The recombinant parathyroid hormone. Denosumab (RANKL inhibitor). Recombinant Calcitonin

DRUGS FOR THE CENTRAL NERVOUS SYSTEM
Multiple sclerosis therapy. Migraine therapy. Anti-CGRP monoclonal antibodies. Alzheimer's disease, biotech drugs in development

DRUGS FOR THE RESPIRATORY SYSTEM
Biotechnological and innovative drugs in asthma therapy. Anti-IgE, Anti-IL5, Anti-IL5 receptor, Anti-IL4 receptor

New molecules or new targets in development for asthma therapy Anti-IL13 / IL17, Anticalins, Aptamers.

Safety of biosimilar drugs.

 

MODULE 2

ADVANCED THERAPIES:
Cells as drugs

GENE THERAPY
Definition and concept of gene therapy. Types of gene therapy approaches. Ex vivo gene therapy. In vivo gene therapy.
The tools of gene therapy. Viruses as safe vectors for gene therapy. The clinical applications of gene therapy. CAR-T. In vivo gene therapy drugs

TARGET THERAPY
Signal transducers. Gene mutations in human tumors. Tyrosine kinase inhibitors. Targeted therapy on the Bcr-Abl protein.

Targeted therapy on EGFR1, HER2 / neu. Inhibitors of VEGF and angiogenesis. RAF and MEK kinase inhibitors. PI3K kinase inhibitors

TARGETED DRUGS IN ONCOLOGY
Development of targeted anticancer chemotherapy. Drugs acting on tyrosine kinase receptors.

EPIGENETIC DRUGS

CLINICAL USE OF BIOTECHNOLOGICAL DRUGS

DRUGS FOR ONCOLOGY
Therapeutic strategies. Monoclonal antibody therapies. Active immunotherapy. Checkpoint inhibitors. Clinical information. Cell-mediated therapies. Cytokine therapies. Inhibitors of IL6. Inhibitors of IL1. Inhibitors of IL12 and IL23. Anti-IL17. Inhibitors of surface antigens of B and T lymphocytes

DRUGS FOR THE IMMUNE SYSTEM
Biotechnological drugs for chronic autoimmune inflammatory diseases. Inhibitors of TNFalpha

ADVERSE EFFECTS of Biotechnological Drugs
Adverse effects related to the mechanism of action. Tumor lysis syndrome. Infections. Tumors. Inhibition of angiogenesis. Adverse immunological effects. Anti-drug antibodies. Immunogenicity. Autoimmune Diseases. Cytokine release syndrome.
Interaction with an antigen other than the target. Toxicity of monoclonal antibody derivatives

Readings/Bibliography

Selected chapters from:

Pharmaceutical Biotechnology, Fundamentals and Applications
Crommelin D.J.A., Sindelar R.D., Meibohm B. Eds, Fifth Edition, Springer

Teaching methods

Frontal lessons

Assessment methods

Verification of learning consists in an oral exam, for each module, which aims to verify and evaluate the achievement of the learning objectives.
The student evaluations takes into account the correctness of the answers, the understanding of the principles learned showed by the student. In addition, the level of exposure, also in relation to the previous knowledge necessary for the understanding of the specific exam subject will be considered. The duration of the oral exam is on average 20-30 minutes.

Teaching tools

PC, Projector. PowerPoint; the slides used during lessons will be available on the VIRTUALE platform

Office hours

See the website of Sanzio Candeletti

See the website of Giulia Sita