Sorry, this has been some time coming but the paper is now online.
Baker D, Ali L, Saxena G, et al. The Irony of Humanization: Alemtuzumab, the First, But One of the Most Immunogenic, Humanized Monoclonal Antibodies. Front Immunol. 2020;11:124. Published 2020 Feb 14. doi:10.3389/fimmu.2020.00124
Alemtuzumab was designed to reduce the immunogenicity of the parent CD52-specific rat immunoglobulin. Although originally marketed for use in cancer (Mabcampath®), alemtuzumab is currently licensed and formulated for the treatment of relapsing multiple sclerosis (Lemtrada®). Perhaps due to its history as the first humanized antibody, the potential of immunogenicity of the molecule has been considered inconsequential, and anti-drug antibodies (ADA) responses were similarly reported as being clinically insignificant. Nonetheless, despite humanization and depletion of peripheral T and B cells, alemtuzumab probably generates the highest frequency of binding and neutralizing ADA of all humanized antibodies currently in clinical use, and they occur rapidly in a large majority of people with MS (pwMS) on alemtuzumab treatment. These ADA appear to be an inherent issue of the biology of the molecule-and more importantly, the target-such that avoidance of immunogenicity-related effects has been facilitated by the dosing schedule used in clinical practice. At the population level this enables the drug to work in most pwMS, but in some individuals, as we show here, antibody neutralization appears to be sufficiently severe to reduce efficacy and allow disease breakthrough. It is therefore imperative that efficacy of lymphocyte depletion and the anti-drug response is monitored in people requiring additional cycles of treatment, notably following disease breakthrough. This may help inform whether to re-treat or to switch to another disease-modifying treatment.
The brilliant DrAngry has come up with a way to see if you are going to stop responding to treatment.
I spoke to a neuro just yesterday about this and they were completely unaware that alemtuzumab induces antibodies against the drug and that this occurs at high frequency. In this study there is a case report to demonstrate that these appear important and stop the drug working.
That’s not all. We have to wait for the slo -poke referees to give you the next installment that suggests we can spot people who won’t respond to the treatment.I guess the regulators should be interested in this, as it is a safety issue
Have a read about the anti-drug responses to alemtuzumab. This is important if you need another dose.
However whats it got to do with fashion? Well the colours used in the manuscript graphs are from colours for Spring 2020 collections. Haved a look at the paper to see what you think!