Antibody Recruiting Molecules (ARM)
A Novel Approach to Immunotherapy in HIV and Cancer Treatment
Nov 14, 2009
The body’s immune system works like a well-developed machine requiring a symphony of cells working together to destroy and stave off infections. When the system fails the result can be disastrous. Immunotherapy uses medications and vaccines to stimulate, augment and initiate the immune system to respond to outside threats.
Antibodies and HIV
The HIV is an elusive virus to the body’s immune system. Researchers recently found that one of the shortfalls of the human immune system against the HIV virus is also one the antibody's stronger point against other viruses; its structure.
An antibody is a Y-shaped molecule with two epitopes (antigen recognizing proteins) on the two Y tips. These two epitopes allow the antibody to bind to two proteins on the antigen's surface, creating a stronger bond when compared to a one-epitope protein bond. (Viruses have proteins sticking off their viral coat; these are the proteins the antibodies bind to).
The HIV has fewer proteins than normal viruses. The proteins are placed far and in between. This structural difference is responsible for the antibody's epitope inability to bind to two different surface proteins making it not as effective (Klein et al. "Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10" Proceedings of the National Academy of Sciences, 2009 Abstract).
Antibodies and Cancer
Antibodies are created when specific T cell recognizes an antigen. Most antigens that invade the body either viruses and bacteria. In response the human body has thousands of different epitopes designed to recognize thousands of antigens. The immune system is very sophisticated in that epitopes do not bind to an individual’s cells. Therefore when cells go rogue like cancer cells, the immune system has a hard time identifying them as foreign. Cancer immunotherapy requires the body to be trained to recognize the cancer cells.
Antibody Recruiting Molecules (ARM)
Yale University’s scientists are working on developing molecules that can recruit antibodies to destroy HIV. The antigen is carried on DNP molecule which the body recognizes as an antigen. The DNP carries a molecule that binds to HIV creating a new complex. This process is two-fold:
- Binding to the virus and blocks the virus from infecting the individual and
- The body’s immune system recognizes the carrier molecule and creates antibodies against it which effectively destroy the virus
(Christopher G. Parker, Robert A. Domaoal, Karen S. Anderson and David A. Spiegel “An Antibody-Recruiting Small Molecule That Targets HIV gp12” J. Am. Chem. Soc., 2009, 131 (45), pp 16392–16394 Abstract).
Antibody recruiting molecules have the potential of being the future of treatment strategies against elusive viruses and cancer. The ARMs have a two-fold advantage; by attaching to viruses or cancer cells they inhibit the antigens' ability to infect or replicate, the binding also flags the immune system to destroy the ARM-antigen complex. The research into the use of immunotherapy to protect against viruses and cancer is very promising.
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