MONOCLONAL ANTIBODIES Drug Delivery.pptx

MONOCLONAL ANTIBODIES Drug Delivery System
Pharmaceutics

1. MONOCLONAL ANTIBODIES PREPARED BY: AMTUL NASEER M.Phil. Pharmaceutics

2. CONTENTS:- INTRODUCTION HISTORY AND DEVELOPMENT OF MONOCLONAL ANTIBODIES PREPARATION EVALUTION APPLICATION

3. 1.INTRODUCTION: What are antibodies ????????

4. ANTIBODIES:- Antibody , also called  immunoglobulin , a protective  protein  produced by the  immune system   in response to the presence of a foreign substance, called an  antigen . Antibodies recognize and latch onto antigens in order to remove them from the body. A wide range of substances are regarded by the body as antigens, including disease-causing organisms and toxic materials such as insect venom.

5. ANTIBODIES:- Antibodies are specialized, Y-shaped proteins that bind like a lock-and-key to the body's foreign invaders — whether they are  viruses , bacteria, fungi or parasites. They are the " search" battalion of the immune system's search-and-destroy system , tasked with finding an enemy and marking it for destruction. " They're released from the cell and they go out and hunt," said Dr. Warner Greene, the director of the Center for HIV Cure Research at the Gladstone Institutes in San Francisco. When antibodies find their target, they bind to it, which then triggers a cascade of actions that vanquish the invader. Antibodies are part of the so-called "adaptive" immune system, the arm of the  immune system  that learns to recognize and eliminate specific pathogens, Greene said.

6. STRUCTURE OF ANTIBODIES:- The four-chain structure of an antibody, or immunoglobulin, molecule. The basic unit is composed of two identical light (L) chains and two identical heavy (H) chains , which are held together by disulfide bonds to form a flexible Y shape. Each chain is composed of a variable (V) region and a constant (C) region Our body has a specialized search-and-destroy army. Antibodies are key players in that fight

7. STRUCTURE OF ANTIBODIES:-

8. Monoclonal Antibodies:- Researchers can design antibodies that specifically target a certain antigen, such as one found on cancer cells. They can then make many copies of that antibody in the lab. These are known as  monoclonal antibodies   ( mAbs or Moabs ). Monoclonal antibodies are man-made proteins that act like human antibodies in the immune system. There are 4 different ways they can be made and are named based on what they are made of…………………..

9. MONOCLONAL ANTIBODIES:- Murine:  These are made from mouse proteins and the names of the treatments end in - omab . Chimeric:  These proteins are a combination of part mouse and part human and the names of the treatments end in - ximab . Humanized:  These are made from small parts of mouse proteins attached to human proteins and the names of the treatments end in - zumab Human:  These are fully human proteins and the names of the treatments end in - umab .

10. HISTORY OF MONOCLONAL ANTIBODIES:- In 1986, Orthoclone OKT3® (muromonab-CD3 ) became the first monoclonal antibody approved by the FDA. Its production was based on the Nobel-winning work of Kohler and Milstein on murine hybridoma technology. This technology, part of which is still used in the generation of some modern monoclonal antibodies, had several steps. The first step involved generating a specific immune response in mice by injecting them with a particular antigen. In the case of muromonab , the antigen was the T-cell co-receptor CD3. This resulted in the mouse’s immune system producing antibodies against CD3. Antibody-producing cells, however, are typically short-lived, and thus not great candidates for the mass production of a therapeutic antibody. To get around this limitation, the second step of the process involved isolating the antibody-producing mouse cells and fusing them with immortalized myeloma tumor cells. This step resulted in the creation of hybrid cells that could produce antibodies but also had the replicative properties of tumor cells.

11. Monoclonal Antibodies:-

12. PREPARATION OF MONOCLONAL ANTIBODIES:-

13. STEPS IN PREPARATION OF MONOCLONAL ANTIBODIES:- Immunize the animal Isolate spleen cells(containing antibody producing B cell) Fuse spleen cells with myeloma cell(using PEG) Allow unfused B cell to die Add aminopterin to culture and kill unfused myeloma cells Clone remaining cells(place 1 cell/wall and allow each cell to grow into a clones of cell) Screen supernatant of each clone for presence of desired antibody Grow chosen clone of cell in tissue culture indefinitely Harvest antibody from the culture $1000-2000 per mg

14. APPLICATIONS OF mAbs :- Advantages of using Monoclonal Antibodies: Hybridoma serves as an immortal source of monoclonal antibody. Same quality of the antibody is maintained amongst the different production batches. Highly reproducible and scalable, unlimited production source. Speed and sensitivity and specificity of assays. Can produce antibodies when needed. No need to worry about maintaining the animals. Antigen or immunogen need not be pure. Selection helps to identify the right clones against the specific antigen

15. APPLICATIONS OF mAbs :- Disadvantages of using Monoclonal Antibodies: Time consuming project - anwhere between 6 months -9 months. Very expensive and needs considerable effort to produce them. Small peptide and fragment antigens may not be good antigens-monoclonal antibody may not recognize the original antigen. Hybridoma culture may be subject to contamination. System is only well developed for mouse and rat and not for other animals. More than 99% of the cells do not survive during the fusion process – reducing the range of useful antibodies that can be produced against an antigen

16. APPLICATIONS OF mAbs :- Disadvantages of using Monoclonal Antibodies: Time consuming project - anwhere between 6 months -9 months. Very expensive and needs considerable effort to produce them. Small peptide and fragment antigens may not be good antigens-monoclonal antibody may not recognize the original antigen. Hybridoma culture may be subject to contamination. System is only well developed for mouse and rat and not for other animals. More than 99% of the cells do not survive during the fusion process – reducing the range of useful antibodies that can be produced against an antigen