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Posted On: 03/24/2020 12:14:58 PM
Post# of 154119
Thanks to Kabonk from a thread at IV; There is plenty of scientific rationale for targeting CCR5 for HIV (entry inhibitor), cancer, GVHD, and as a treatment for COVID-19.
CCR5 is a receptor on many immune cells, including CD4+ T-cells, TRegs, and macrophages, to name a few. CCR5 inhibition is a potent method of immunomodulation. Leronlimab mAB against CCR5 has a different action than small molecule inhibitors of CCR5 like maraviroc, making it less toxic.
CCR5 is a receptor on TRegs. Inhibiting CCR5 activation inhibits TRegs from migrating into areas of inflammation, thus keeping the immune system revved up against the virus, and against cancer. It tilts the immune system towards effector cell function to attack pathogens and cancer.
Leronlimab acting on CCR5 on macrophages will block many of the inflammatory cytokines, such as TNF, IL-6, IL-13, potentially limiting the lethal cytokine storm that kills in COVID-19.
https://www.jimmunol.org/content/jimmunol/176...8.full.pdf
They also demonstrate that CCR5 neutralization or a deficiency of CCR5 significantly decreases IL-13-induced inflammation, alveolar remodeling, structural and inflammatory cell apoptosis, and respiratory failure and death.
So, there are two proposed mechanisms of action against SARS-CoV-2: limiting TRegs, and limiting the cytokine storm in the lungs. Will see if it helps or not. 4 COVID19 patients have been treated with it so far under emergency use, and a trial is forthcoming.
Posting again the rationale for targeting CCR5 in cancer:
https://cancerres.aacrjournals.org/content/79/19/4801
CCR5 is a receptor on many immune cells, including CD4+ T-cells, TRegs, and macrophages, to name a few. CCR5 inhibition is a potent method of immunomodulation. Leronlimab mAB against CCR5 has a different action than small molecule inhibitors of CCR5 like maraviroc, making it less toxic.
CCR5 is a receptor on TRegs. Inhibiting CCR5 activation inhibits TRegs from migrating into areas of inflammation, thus keeping the immune system revved up against the virus, and against cancer. It tilts the immune system towards effector cell function to attack pathogens and cancer.
Leronlimab acting on CCR5 on macrophages will block many of the inflammatory cytokines, such as TNF, IL-6, IL-13, potentially limiting the lethal cytokine storm that kills in COVID-19.
https://www.jimmunol.org/content/jimmunol/176...8.full.pdf
They also demonstrate that CCR5 neutralization or a deficiency of CCR5 significantly decreases IL-13-induced inflammation, alveolar remodeling, structural and inflammatory cell apoptosis, and respiratory failure and death.
So, there are two proposed mechanisms of action against SARS-CoV-2: limiting TRegs, and limiting the cytokine storm in the lungs. Will see if it helps or not. 4 COVID19 patients have been treated with it so far under emergency use, and a trial is forthcoming.
Posting again the rationale for targeting CCR5 in cancer:
https://cancerres.aacrjournals.org/content/79/19/4801
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