Someone over at stocktwits doubted the efficacy of leronlimab compared to Trodlevy. Here were my responses.
A response to someone else who wasn't sure of leronlimab's mechanism.
Quote:You yammer on that people don't know anything about leronlimab and opine about how leronlimab cannot be better than Trodelvy yet you know nothing about leronlimab or the CCR5 receptor. You are speaking out of ignorance.
Trodelvy is no doubt a good drug, but it's also a one trick drug. Corrupting DNA cleavage and causing cell death is a neat trick the problem that develops is resistance to the drug. That resistance is why Trodelvy's numbers are not better than they are.
Leronlimab on the other hand has multiple attack vectors.
Leronlimab - inhibits angiogenesis, anti-trafficking of tumor cells, increase in tumor fighting NKT cells, debases DNA repair, stops the recruitment of Tregs to tumor sites (Tregs promote tumor immunity), downregulates IL-13 a tumor protectant, IL-4 (IL-4 promotes tumor immunity), upregulates IFN-gamma promoting tumor cell death and downregulates PD-L1. Downregulates CDK2/4/6, cyclin D1, cyclin E, and PCNA which are implicated in tumor cell growth. Upregulates p27 and p53 which are both tumor suppressors.
It has been shown that CCR5 blockade in combination with a topoisomerase inhibitor can increase the action of the topoisomerase inhibitor multiple fold. It does so by reducing cell ability to repair DNA damage. Trodelvy is one of the few drugs that may actually enhance leronlimab's ability to fight cancer.
A response to someone else who wasn't sure of leronlimab's mechanism.
Quote:Actually maraviroc is a small molecule that nestles within the CCR5 receptor and changes it's shape which makes it harder for HIV and cytokines to bind. Leronlimab is a large molecule that bind to sites that both HIV and cytokines bind to blocking them from binding. That complete blockade of binding when 100% receptor occupancy is achieved is what makes leronlimab superior.
So it's leronlimab that completely stops CCR5's functionality. But the other CCR receptors also bind CCR5 ligands but there are few compared to CCR5. With an immune challenge the other receptor numbers increase which can bring immune homeostasis rather than an overactive response if CCR5 is blocked.
Any CCR5 blocker will reduce DNA repair and make Trodelvy more effective. In the case of maraviroc it increases Trodelvy's potency by 4 times. With leronlimab's increased effectiveness it should be higher.
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