As Greg Winter from Cambridge got the Nobel Prize for his part in the making of antibodies, notably humanizing antibodies, we can celebrate his work on the production of the world's first humanised antibodies (CAMPATH-1H) that was designed to stop anti-antibody responses , which were common when rodent antibodies were used.
Although it achieved its aim somewhat....It is in fact probably one of the Worlds worse antibodies for inducing an anti-drug response.
Did these stop the drug working?
The antibody depletes most T and B cells from the blood, but also it depletes regulatory cells and when the immune system reconstitutes, it is amazing that there is a massive anti-drug response. However this does not seem to matter because the drug is gone by the time it arrives and it generally wanes by 12 months. So these do not interfer with the next round of treatment. In addition to binding antibodies there are neutralizing antibodies that can stop the drug working.
However, the presence of neutralizing antibodies was not mentioned in the European licence, until after we identified them.
Alemtuzumab depletion failure can occur in multiple sclerosis.
Dubuisson N, Baker D, Kang AS, Pryce G, Marta M, Visser LH, Hofmann WE, Gnanapavan S, Giovannoni G, Schmierer K.
Immunology. 2018;154(2):253-260.
In the MS-CARE I and MS-care II trials binding antibodies occurred in about 60% of people within the first month of infusion and these were boosted by repeat injections. It meant that over 60% of people had an antibody binding response after 23-23months. Of these about 30% of people had neutralizing antibodies at the end of the second treatment cycle. This may suggest that some people may not deplete properly and so the drug would not work.
We approached the manufacturer for the data over and over again and none was forth coming.
So to shut me up at ECTRIMS we have
P611 - Minimal impact of anti-alemtuzumab antibodies on the pharmacodynamics and efficacy of alemtuzumab in RRMS patients from the CARE-MS studies