View
226
Download
4
Category
Tags:
Preview:
Citation preview
MONOCLONAL ANTIBODIES
As therapeuticsAs diagnosticsAs targeting agents
INTRODUCTION
Have remarkable specificity Single specificity -> promising in human
therapy Widely used as diagnostic & research
reagents
MANUFACTURING OF MONOCLONAL ANTIBODIES
Monoclonal antibodies are traditionally made from mice or rats that have been immunized with the desired antigen
CONVENTIONAL METHOD FOR MAKING mAbs
Clinical Uses for Monoclonal Antibodies
In vitro diagnostic agents In vivo imaging agents Therapeutic agents (MAb works like a
drug) Targeting agents (MAb linked to toxin)
Monoclonal Antibodies as in vitro Diagnostic Agents
Detects the presence, absence or relative amount of protein.
MAbs work nicely because they bind very specifically to the protein.
Example: Pregnancy tests. MoAb detects elevated levels of HCG in the urine. High level of HCG is produced by placenta in the early stages of pregnancy.
ELISAEnzyme
produces
Color
Enz
Monoclonal Abs on Therapeutics
Suppressing The immune system Killing Malignant cells
59 MAbs currently in clinical trials 31 for cancer therapy
SUPPRESSING THE IMMUNE SYSTEM
Monoclonal antibodies specific to the different receptors of various cells are used to prevent the normal usage of these receptors.
First MAb on market was OKT3, a murine MAb
used to prevent renal transplant rejection
• Orthoclone OKT3 targets T-lymphocytes surface antigen CD3 reversal of acute kidney transplant rejection.
SUPPRESSING THE IMMUNE SYSTEM
Problems with Mouse Ab in Humans
Human immune response to mouse antibodies (HAMA-Human Anti-Mouse Antibodies) – Endanger the patient and enhance the
clearance of the Ab and reduce its therapeutic effect.
Mouse antibodies do not activate human complement system or Ab-mediated cytotoxicity
To Overcome this Problem
Hybrid monoclonal antibodies have been made by recombinant DNA technology
Types of MAbs
Mouse Chimeric
Blue: Mouse sequencesRed: Human sequences
Humanized Human
MOUSE Fv region
MOUSE CDR
Regions “A”
Mutagenesis
“ B”
SUPPRESSING THE IMMUNE SYSTEM
•Zenapax (Daclizumab) targets Alpha-chain of IL-2 receptor (CD25) of T- lymphocytes. prevention of acute kidney transplant rejection.
• Remicade (Infliximab) targets tumor necrosis factor-alpha (TNF-α) treatment of Crohn’s disease & rheumatoid arthritis.
•Xolair (Omalizumab) targets IgE preventing the binding of IgE to mast cells against allergic asthma.
Zenapax: Humanized Monoclonal Antibody
• Mouse amino acids - Red• Human amino acids -White• Prevents rejection in kidney transplantations
Clinical trials with Infliximab… A chimeric Mab against TNF:
Results showed a significant clinical improvement Results showed a significant clinical improvement in all Infliximab doses.in all Infliximab doses.Treatment is usually given together with Treatment is usually given together with methotrexate.methotrexate.
TO KILL MAGLIGNANT CELLS
Tumors have antigen on the surface that are specific to themselves.
They are also more highly expressed than normal.
Monoclonal antibodies used to target these tumors specific antigen (TSA)
TO KILL MAGLIGNANT CELLS
TO KILL MAGLIGNANT CELLS
Mabthera/Rituxan (Rituximab) targets CD20 surface antigen of B-lymphocytes treatment of non-Hodgkin’s lymphoma. Herceptin (Trastuzumab) targets Human epidermal growth factor-like receptor 2 (HER-2) treatment of metastatic breast cancer over expressing HER-2 protein. The only monoclonal so far that is effective against solid tumors. MabCampath (Alemtuzumab) targets B-lymphocytes CD52 treatment of B-cell chronic lymphocytic leukemia. Complete remission up till now.
MAbs: Site-directed Targeting Agents
Link a toxic drug, protein or radioisotope to an MAb with a high specific affinity for a tumor-associated antigen.
Toxin
XX
Toxin
Cancer cellexpressing tumor antigen
CONCLUSION
Monoclonal Antibodies used as in vitro Diagnostic Agent In vivo imaging agents Therapeutics agents
Supressing immune systemKilling Malignant cells
Targeting Agents (MAb linked to toxin)
Recommended