84921 - Molecular Pharmacology and Pharmacotherapy of the Biotechnological Drugs

Learning outcomes

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

Course contents

GENETIC ENGINEERING AND RECOMBINANT DNA
Gene cloning. Cellular genetic engineering for the production of protein-drugs. DNA transfer methods in cultured cells. Cellular 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 research, development and production of drugs
MONOCLONAL ANTIBODIES
Antibody structure. Antibody activity and recycling. Biotechnological synthesis of antibodies. Growth and selection of hybridomas. Chimeric, humanized and fully human monoclonal antibodies. Changes that improve properties
pharmacological effects of monoclonal antibodies. Antibodies conjugated to small molecules
ADVANCED THERAPIES: GENE THERAPY
Definition and concept of gene therapy. Types of approaches to gene therapy. Ex vivo gene therapy. In vivo gene therapy.
The tools of gene therapy. Viruses as safe vectors for gene therapy. 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 Bcr-Abl protein.
Targeted therapy on EGFR1, HER2 / neu. VEGF and angiogenesis inhibitors. RAF and MEK kinase inhibitors. PI3K kinase inhibitors

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

pharmacodynamic
Mechanisms of action of monoclonal antibodies. Antibodies directed towards tumor antigens. Modification of the body's response. Mechanisms of action in non-anticancer therapies. Monoclonal antibodies conjugated with agents
Cytotoxic. Selectivity of action. Side effects of monoclonal antibodies.

Pharmacokinetics
Routes of administration of biotechnological drugs. ADME. Salvage pathway. Antigen properties. Immunogenicità77

ADVERSE EFFECTS
Adverse effects related to the action mechanism.Tumor lysis syndrome. Infections. Tumors. Inhibition of angiogenesis. Immunological adverse effects. Anti-drug antibodies. Immunogenicity. Autoimmune diseases. Cytokine release syndrome. 9.4
Interaction with an antigen other than the target. Toxicity of monoclonal antibody derivatives 298
Drug-antibody conjugates.

CLINICAL USE OF BIOTECHNOLOGICAL DRUGS

DRUGS FOR ONCOLOGY
Therapeutic strategies. Therapies with monoclonal antibodies. Active immunotherapy. Checkpoint inhibitors. Clinical information. Cell-mediated therapies. Cytokine therapies. IL6 inhibitors. IL1 inhibitors. IL12 and IL23 inhibitors. Anti-On 17. Inhibitors of surface antigens of B and T lymphocytes

DRUGS FOR THE IMMUNE SYSTEM
Biotechnological drugs for chronic autoimmune inflammatory diseases. TNFalfa inhibitors

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

Bone and calcium metabolism diseases.
The recombinant parathyroid hormone. Denosumab (RANKL inhibitor). Recombinant calcitonin

DRUGS FOR THE CENTRAL NERVOUS SYSTEM
Multiple sclerosis therapy. Migraine therapy. Monoclonal anti-CGRP antibodies. Alzheimer's disease, biotechnological drugs in development

DRUGS FOR THE RESPIRATORY SYSTEM
Biotechnological and innovative drugs in the treatment of asthma. Anti-IgE, Anti-IL5, IL5 anti-receptor, IL4 anti-receptor
New molecules or new targets in development for the treatment of asthma Anti-IL13 / IL17 , Anticaline, Aptameri.

Safety of Biosimilar drugs

Readings/Bibliography

Elisabetta Vegeto Adriana Maggi Paola Minghetti

Farmaci biotecnologici: aspetti farmacologici e clinici. Casa Editrice Ambrosiana. Zanichelli

Teaching methods

The course is organized in lectures.

Assessment methods

MOLECULAR PHARMACOLOGY AND PHARMACOTHERAPY OF BIOTECHNOLOGICAL DRUGS module

The verification methods of learning take place through an oral interview. This interview aims to check knowledge on the topics covered during the lessons of the module.
The purpose of the test concerns the candidate's ability to have learned the bases of production, development and mechanisms of action and ADME of biotechnological drugs.

The duration of the oral test is on average 20-30 minutes.

The student presents the answers to the questions to the exam commission. For each question asked, an assessment is made based on the correctness of the answers, the demonstrated understanding of the principles learned and the level of exposure, also in relation to the different parts of the program as well as previous knowledge, necessary for understanding the specific subject exam.

Teaching tools

PC. Projector.PowerPoint.  Presentations of the lessons will be available on IOL Platform.

Office hours

See the website of Gabriele Campana