Several readers have written comments on the previous blog entry. Thank you! For those interested in summer recommendations, I am currently reading “Mindset.” I think it’s a psychology classic. Of particular interest to me are the sports comparisons. John McEnroe’s description is remarkable. Carol Dweck, the author of “Mindset,” published in Nature, a nerdy version of her research applied to the educational environment.
This week I want to cover the basics of some immunotherapy strategies in different human diseases. Monoclonal antibodies are proteins that have the function of blocking the action of microorganisms and defending us from infection. They have two light chains and two heavy chains organized in a variable region and a constant region. Within the variable area, there is a segment known as the hypervariable region where the antibody binds to its particular antigen. The constant part is involved in some effector actions such as macrophage activation and initiation of the complement cascade. Due to their high specificity, antibodies are one of the most versatile tools available to physicians today to treat autoimmune diseases and cancer.
The original technique to produce monoclonal antibodies (abs) based on hybridomas (fusion of lymphocytes and myeloma cells) was designed in the seventies by Cesar Milstein and George Kohler. Sir Gregory Winter and his research group established modern processes for generating abs using recombinant DNA technology.
According to their origin abs can be:
- Murine: All the protein is from a mouse. One way to identify them is by the mo suffix. For example, muromonab, anti-CD3 used in the treatment of rejection of some types of corticoid-refractory transplants.
- Chimeric antibodies: The variable region is human, and the rest comes from a mouse sequence. The suffix xi identifies chimeric antibodies. An excellent example is rituximab, anti-CD20, the basis of therapy in several types of lymphoma.
- Humanized antibodies: The hypervariable region with the antigen-binding site contains a human sequence, and the rest is of mouse origin. They have the suffix zu as trastuzumab, anti-HER2 fundamental for the management of some breast and stomach tumors.
- Human antibodies: All the sequence of the antibody is of human origin. They have the suffix u as adalimumab, anti-TNF indicated in several autoimmune diseases such as rheumatoid arthritis, psoriasis, etc.
In the next blog entry, I will comment on some modifications to the basic structure of an antibody with therapeutic potential (BITEs, nanobodies, etc.).
To finish, another recommended book. It is a story about a meeting over a beer. About 1975, a finance wizard and a biologist met in a bar in San Francisco to talk about business. The biologist was not very motivated to attend because he was disappointed with his previous experiences trying to market an idea originating in his laboratory. The entrepreneur was persistent and came up with good proposals. The meeting, scheduled for 30 minutes, lasted most of the afternoon. Several beers later, Robert Swanson and Herbert Boyer agreed on the basis for founding Genentech. The full story is beautifully described in this enjoyable book. One beer can change a life! See you next time!