Science: Reveals the mechanism by which therapeutic antibodies bind to human CD20.

August 18, 2020 /--- Since the late 1990s, immunotherapy has been the first line of treatment to combat lymphoma, using synthetic antibodies to prevent the proliferation of cancerous white blood cells.
, however, little is known about the molecular mechanisms of the therapy, which has been in use for more than 20 years.
new study, researchers from France's National Centre for Scientific Research, the Pasteur Institute and the University of Bordeaux observed for the first time the interaction between therapeutic antibodies and their target proteins.
described these molecular mechanisms, opening the way for the development of new treatments.
study was published in the August 14, 2020 issue of the journal Science under the title "Binding mechanisms of therapeutic antibodies to human CD20".
picture from Nicolas Reyes.
hodgkin's lymphoma is one of the most common cancers, affecting nearly 1.5 million people worldwide.
cause B lymphocytes, a type of white blood cell, to proliferate uncontrolled, damaging healthy cells.
since the late 1990s, immunotherapy using synthetic antibodies to target a protein called CD20 on the surface of B lymphocytes has been a first-line treatment.
the body's defenses identify these antibody-binding cells as pathogens and destroy them.
, they can be divided into two categories, depending on the number of therapeutic antibodies binding to CD20 molecules and the immune response they trigger.
the interaction between the first class of therapeutic antibodies (type 1 therapeutic antibodies) and CD20 molecules is twice that of the second class of therapeutic antibodies (type 2 therapeutic antibodies), which can trigger a cascading immune response called the "complement pathway".
, the molecular mechanisms of the differences between the two therapeutic antibodies were unclear.
using cryogenic electroscopy, the researchers were able to observe for the first time the interaction between these two therapeutic antibodies and their target molecules at the atomic level.
found that, due to the availability of space, the CD20 protein could bind to two therapeutic antibodies, but only to one type 2 therapeutic antibody.
because of the large number of therapeutic antibodies type 1 on the surface of B lymphocytes, they can form clusters.
confirmed that these clusters trigger a complement pathway, which can lead to damage to target B lymphocytes.
other hand, therapeutic antibodies type 2 are sparsely dispersed on the surface of B lymphocytes and therefore do not trigger this cascading immune response.
other independent immune responses can still destroy these cells.
has never been more accurate in describing the mechanism of therapeutic antibodies.
could lead to the development of new synthetic antibodies that control the immune response in patients.
, the description of the molecular mechanisms that activate the complement pathway opens up new research possibilities for understanding how immune defense systems work.
(bioon.com) Reference: 1.Anand Kumar et al. Binding mechanisms of therapeutic antibodies to human CD20. Science, 2020, doi:10.1126/science.abb8008.2.The behavior of therapeutic antibodies in immunotherapy.