Monoclonal antibodies: treating cancer with immunotherapy
“The first revolution was the development of monoclonal antibodies more than 20 years ago. This idea of building molecules that the immune system produces naturally allowed the pharmaceutical industry to offer antibodies as therapeutic solutions,” observes the physician-scientist Vassili Soumelis.
Monoclonal antibodies are molecules that are naturally produced by the immune system to trigger a targeted attack on a danger that has already been encountered. It soon became clear that, if well chosen, these “homing missiles” could not only identify tumor cells, but could also block their growth. This is true of trastuzumab (Herceptin®), an antibody that attaches to the HER-2 protein on the surface of the tumor cells in around 15% of women suffering from breast cancer. Acting as a switch, trastuzumab blocks the action of its membrane receptor, which inhibits growth of the tumor. It has broadly improved the vital prognosis of these patients since the early 2000s.
Identical strategies have been developed, in particular for treating lymphoma, using retuximab, for ENT and colon tumors with antibodies that target the EGF (Epidermal Growth Factor) receptor. The vascularization required for development can also be targeted with an antibody aimed at VEGF (vascular endothelial growth factor), bevacizumab, or Avastin®, to block the growth of many tumors (in the lung, breast, colon and elsewhere).
Another idea that is starting to gain ground is the use of antibodies to carry a therapeutic molecule – chemotherapy or a radioactive product.
“The presentation of the results of the EMILIA trial assessing the effectiveness of the T-DM1 molecule, combining trastuzumab with chemotherapy in patients with breast cancer that overexpresses HER-2, was one of the major focuses in oncology in 2012,” recounts Christophe Le Tourneau. Just like Herceptin®, T-DM1 attaches to HER2 and blocks the proliferation of the tumor cells, but it also delivers a chemotherapy agent directly into the cancerous cells.
Targeting the interleukin pathway
Interleukin 2 (IL-2) is already used to treat certain types of cancer. The translational immunotherapy team of Eliane Piaggio plans to use antibodies to change the signaling cascade induced by IL-2 g, with financial backing from the Agence Nationale de la Recherche. As soon as it develops the first humanized anti-IL-2 antibodies, her team plans to study the activation of the immune system using an IL-2/anti-IL-2 complex.
There are a number of approaches that use antibodies, and these offer new solutions for cancer treatment. There are many options to be explored, developed and personalized through the collaboration of physicians, biologists and chemists. Progress will no doubt be achieved through the combination of several therapeutic strategies.