April 30, 2008
Fast Cloning For Monoclonal Antibody Production
Vaccination is slow compared to a rapid biotech process to harness your immune cells to produce antibodies.
Vaccines push the immune system to create defenses against illness, but they take time to work. A new process developed by scientists at the Oklahoma Medical Research Foundation (OMRF) and Emory University stands to revolutionize the process.
In an advance online publication in Nature, the researchers describe a method that can identify and clone human antibodies specifically tailored to fight infections. The new technology holds the potential to quickly and effectively create new treatments for influenza and a variety of other communicable diseases.
These press releases do not go into much detail about exactly what these researchers did. But they must have a way to rapidly identify and separate out immune cells that are especially reactive to an infectious agent.
Imagine massive production of antibodies within a few weeks of the start of a deadly influenza pandemic.
"This method could find broad application towards almost any infectious disease," says Rafi Ahmed, PhD, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.
As a first example, doctors could quickly generate human antibodies against a pandemic flu strain as a stop-gap therapy or to protect people from infection. In this study, the antibodies were not tested on influenza virus strains with pandemic potential, such as the H5N1 strain although such studies are underway.
Ahmed and postdoctoral fellow Jens Wrammert, PhD, from the Emory Vaccine Center and Emory University School of Medicine, collaborated with Don Capra, PhD, and Patrick Wilson, PhD, immunology researchers at the Oklahoma Medical Research Foundation.
"With just a few tablespoons of blood, we can now rapidly generate human antibodies that can be used for immunization, diagnosis and treatment of newly emerging strains of influenza," Wilson says. "In the face of a disease outbreak, the ability to quickly produce infection-fighting human monoclonal antibodies would be invaluable."
They clone the genes involved in making the desired antibodies.
The methods previously used to make human monoclonal antibodies can be relatively laborious, Ahmed says. They involve sifting through human B cells and looking for those that make the right antibodies, or vaccinating mice and "humanizing" the mouse antibody genes by altering them so that they resemble human antibodies.
To make human antibodies against influenza, the Emory and University of Oklahoma researchers isolated antibody-secreting cells (plasma cells) from volunteers' blood a week after vaccination and cloned the antibody genes from these antibody-secreting cells.
With an otherwise well functioning immune system the monoclonal antibodies would be useful for treating life threatening diseases. But for an aged immune system how much benefit would the antibodies provide?
"With an otherwise well functioning immune system the monoclonal antibodies would be useful for treating life threatening diseases. But for an aged immune system how much benefit would the antibodies provide?"
Uh... like massive benefit... The failure of an aged immune system is precisely the inability to bring to the fore a tailored antibody response of sufficient magnitude. Even aged immune systems retain sufficient cellular capacity to mop up provided the viral attack is quenched by sufficient antibody.
Did you mean something else when you wrote the above quote?
I want the mariginal costs for monoclonal antibodies to be reduced. I think that would help stop medical inflation. Does provide the means do that? I remember reading a paper that biologics genericization would not significantly lower their costs.
But would this method of using antibodies cause the bacteria to develop resistance? After all, bacteria are known to become resistant to antibiotics, and there are many new strains of tuberculosis that can defeat most antibiotics. I worry that the same thing will happen when antibodies are used as antibiotics.
Yes, I think this will cause an increase in the rate of evolution among pathogens. However, what's more important is the pathogens' rates of evolution will remain governed by natural processes while our rate of response will increase by many orders of magnitude.
Pathogens will have a tendency to evolve toward less lethality. A new strain of staph or influenza that kills people will get immediate treatment with custom tailored antibodies. A new strain of staph or influenza that causes a day or two of missed work won't attract the same kind of response.
Also, because antibodies are tailored to an already identified threat, they are less likely to lead to irresponsible prophylactic, broadcast or placebo use as was the case with antibiotics.
I was thinking a few things when I wrote that:
1) Do the immune cells that respond to antibodies bound to antigens really not age as fast as immune cells that produce antibodies?
2) Aside from pathogen attacks humans suffer in at least 3 other ways as a result of an aging immune system:
A) More auto-immune attacks.
B) Less about to "take out the trash" of intercellular debris.
C) Less ability to snuff out cancer cells at a very early stage.
I would expect these antibodies to only address 2-B.
So I am thinking that we really need full immune system rejuvenation.
But would this method of using antibodies cause the bacteria to develop resistance?
If the bacteria or viruses were going to become immune to antibodies in general, they would have done so by now.
They already evade antibody attacks by changing signatures; flu and cold viruses can go around every year because the immunity from the last infection isn't good against the current crop. But this is different. The antibody would be tailored to the new strain just a few weeks old, giving it far less time to change signatures.
That's crucial. With a sufficiently fast response, the evolving strain could be snuffed out before it has a chance to reach many hosts or recombine with other viruses. This could slam the door shut on pathogen evolution and perhaps make some types go extinct.
Imagine maladies from bacterial pneumonia to the common cold going the way of smallpox.
> aging immune system:
> A) More auto-immune attacks.
> I would expect these antibodies to only address 2-B.
There are already available monoclonal antibody-based treatments for auto-immune attacks (i.e. psoriasis and such).