Quote:Now to say the complete opposite (that LL completely blocks CCL5 and CCL2 binding to CCR5 so it has no immune capability) may not be completely true. Maybe it's a question of dosing or semantics in what you are saying.
Agree with you that LL blocks "normal" immune system to some extent by blocking CCL5 and CCL2 from binding to CCR5, but only at higher doses.
The interesting thing is that we *want* to block CCL5 and CCL2 from binding to CCR5 in cancer and anti-inflammatory / immune dampening indications. Cytodyn had it all wrong for years by claiming that it didn't do this. 2D7 antibody was much better at blocking CCL2/RANTES activation at lower doses (8 fold lower) than PA14/LL in these early studies.
A few months after I posted here that it was wrong that there was normal immune function in CCR5 that leronlimab had bound Cytodyn finally took that claim down from their website. Of course it's a matter of dosage. At doses much less than 700mg you don't have 100% receptor occupancy and if leronlimab is not occupying CCR5 than that receptor will have normal immune function.
Maraviroc allosterically binds to CCR5 which is a shallow attachment that changes the chape of the CCR5 receptor to stop binding by HIV or chemokines and does not attach to the n-terminus. That may allow some binding or even dislodgement in some cases. Leronlimab binds orthosterically, deep pocket including the n-terminus and blocks HIV and chemokines by physically occupying the sites that they use for attachments. There is going to be no immune activation where leronlimab is bound.
As I've explained before immune activation by CCLs occurs at other CCR receptors which bind the same chemokines as CCR5. They would be more numerous than normal in any disease state. Which brings about a measured immune response rather than an overactive immune response.
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