are the mAb consider goo immunogen or tolregen
are they have high or low antigenicity if they human nature
after answer so why more than half of patients treated with immune checkpoint inhibitors develop resistance
Hi
You're questions touch many different problems.
- all mAbs may provoke anti-drug antibodies synthesis (ADA) even if they are fully human or humanized
- ADA not always must be neutralizing (strong ADA binding with mAb prevent mAb binding to target)
- ADA not always must be clearing (strong ADA binding with mAb may be entry to immune complexes formation which is recognized by the immune system - total body clearance of the drug rising and concentration of free mAb in serum decreasing and affect clinical effectiveness of the therapy)
- immunogenicity of mAbs not always must have a negative impact on treatment
- in the case of some approved therapeutic mAbs effect of tolerance was seen (for example ustekinumab). The nature of this effect is not fully understood (Treg, depletion by Mreg activated T cells, interaction with FCGRIIB receptor etc). Some mAbs have a strong suppressive effect on the immune system, which can also cause immunotolerance to the drug.
- typical interaction of the therapeutic mAbs with the immune system cover activation and suppression processes it is some kind of continuum.
Your last question covers a very important message. We know a lot about how mAb's work, what is the mechanism of action, and what is the mode of action. We don't know everything about them, but we know quite a lot about their pharmacology. Unfortunately, we cannot say the same for autoimmune diseases, for example. We still know too little to say about proposed pharmacological methods as the perfect approach. Due to the fact that the etiopathogenesis of these diseases is often still unclear, the currently used drugs usually achieve the effect only in part of the patient's population. It is a good approach to stratify patients prior to treatment, whenever possible. Thanks to the initial selection in some types of diseases, it is possible to determine whether the patient can be classified as a responder or not.
Best regards
Tomasz
You might find this review helpful for why patients acquire resistance to ICI https://pubmed.ncbi.nlm.nih.gov/32289269/
Jamie Wallis really thanks for redirected me to this full articles
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