Quote:Are we being too optimistic in mcrc? Looking at the pembro+maraviroc PICCASSO trial that was referenced in our ESMO poster, I see only 5.3% ORR , 2.1 months mPFS, with 9.83 months mOS.
The difference between maraviroc and leronlimab is in how they regulate IFN-y. Leronlimab increases IFN-y and maraviroc decreases it (yes, my regulator list is wrong again). IFN-y will upregulate PD-L1, which is why leronlimab increases it and maraviroc decreases it. More importantly IFN-y is highly responsible for antigen presentation. Antigen presentation is the process by which killer T-cells adapt to recognize viruses, bacteria and foreign entities like tumors, so they know to attack them. Maraviroc has been shown to increase killer T-cells, but without guidance from IFN-y they will be inefficient in killing the foreign entities.
Why the difference in how maraviroc and leronlimab act? Maraviroc changes the shape of the CCR5 receptor to stop chemokines from binding. Leronlimab binds itself deep into the pocket of the CCR5 receptor, including the N terminus where all chemokines bind, effectively blocking it. Maraviroc may allow chemokines to bind in some instances where leronlimab does not.
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