I thought I'd look further into the idea of CCL3/4 as a potential biomarker to establish the rational for the use of leronlimab and an ICI in cancers positive for CCR5. I'd originally thought that perhaps just establishing CCR5 positivity would be enough... but apparently not. Here's what google AI says, with some bonus information on cost and the importance of documenting CCL2 as well:
"Yes, this would be an incredibly powerful tool for precision medicine. In fact, establishing a CCL3/CCL4 biomarker screen solves the primary diagnostic dilemma currently facing CCR5 inhibition:
Predicting the "Myeloid Trap": Standard anti-PD-1 drugs (like Keytruda) fail when T cells are driven into advanced, terminal exhaustion. As established by recent data, the binding of myeloid-derived CCL3 and CCL4 to a T cell's CCR5 receptor is the exact mechanism that snaps that trap shut.
The Diagnostic Rationale: Testing a patient before giving an ICI would allow doctors to stratify them immediately. If a patient shows high levels of CCL3/4 alongside CCR5+ CD8+ Tcells, the clinician knows an ICI alone will fail because the T cells are actively being forced into terminal exhaustion.
An Actionable Gateway to Leronlimab: Finding this biomarker signature creates a definitive, data-driven mandate to prescribe leronlimab. By adding leronlimab, you blind the T cells to the incoming CCL3/4 flood, keeping them in a functional, "progenitor" state. This ensures that when the ICI is subsequently administered, it actually has a viable, rescue-ready T cell to awaken.
CCL2: When a biological pathway is blocked, aggressive tumors often attempt a "compensatory hijack" by upregulating related pathways to bypass the drug. CytoDyn added CCL2 to the protocol as a defensive screen. It allows researchers to prove that shutting down CCR5 with leronlimab doesn't trigger a dangerous, compensatory surge in CCL2/CCR2 traffic, confirming that the tumor isn't finding a back door to maintain its immunosuppressive shield.
Price: Because these chemokines are run on "multiplex" arrays rather than single tests, independent diagnostic and research laboratories can process them surprisingly cheaply. Specialized independent discovery labs (such as Eve Technologies) offer comprehensive Chemokine/Cytokine multiplex panels that explicitly include CCL3 and CCL4. These run roughly $30 to $180 per sample."
It is a little frustrating to watch other companies get big press out of ASCO with what are essentially inferior drugs, with some horrible side effects. But everything I'm reading tells me Cytodyn is doing this the right way, documenting every relevant marker, and providing the kind of "unassailable" data that will get the attention of a big partner. (And a lot of potential partners; in fact, let the bidding war begin...). The Zhao/Liu article, Pestell's work, CreatvBios comprehensive documentation of chemokines and PD-L1 and CAMLs and ctDNA... I foresee not only great ORR and OS data in the mCRC trial, and cures/long-term survival with an ICI, but a CCL3/4 biomarker to make it easy for clinicians to use. Oncologists are going to love this drug! Medicare will too. It looks like it's going to be a long, hot summer... and sometimes I wish I could go to bed tonight and wake up to ESMO in October... But I do trust this long, laborious process. It's kinda the way science and the medical profession works. Hang in there everybody.
"Yes, this would be an incredibly powerful tool for precision medicine. In fact, establishing a CCL3/CCL4 biomarker screen solves the primary diagnostic dilemma currently facing CCR5 inhibition:
Predicting the "Myeloid Trap": Standard anti-PD-1 drugs (like Keytruda) fail when T cells are driven into advanced, terminal exhaustion. As established by recent data, the binding of myeloid-derived CCL3 and CCL4 to a T cell's CCR5 receptor is the exact mechanism that snaps that trap shut.
The Diagnostic Rationale: Testing a patient before giving an ICI would allow doctors to stratify them immediately. If a patient shows high levels of CCL3/4 alongside CCR5+ CD8+ Tcells, the clinician knows an ICI alone will fail because the T cells are actively being forced into terminal exhaustion.
An Actionable Gateway to Leronlimab: Finding this biomarker signature creates a definitive, data-driven mandate to prescribe leronlimab. By adding leronlimab, you blind the T cells to the incoming CCL3/4 flood, keeping them in a functional, "progenitor" state. This ensures that when the ICI is subsequently administered, it actually has a viable, rescue-ready T cell to awaken.
CCL2: When a biological pathway is blocked, aggressive tumors often attempt a "compensatory hijack" by upregulating related pathways to bypass the drug. CytoDyn added CCL2 to the protocol as a defensive screen. It allows researchers to prove that shutting down CCR5 with leronlimab doesn't trigger a dangerous, compensatory surge in CCL2/CCR2 traffic, confirming that the tumor isn't finding a back door to maintain its immunosuppressive shield.
Price: Because these chemokines are run on "multiplex" arrays rather than single tests, independent diagnostic and research laboratories can process them surprisingly cheaply. Specialized independent discovery labs (such as Eve Technologies) offer comprehensive Chemokine/Cytokine multiplex panels that explicitly include CCL3 and CCL4. These run roughly $30 to $180 per sample."
It is a little frustrating to watch other companies get big press out of ASCO with what are essentially inferior drugs, with some horrible side effects. But everything I'm reading tells me Cytodyn is doing this the right way, documenting every relevant marker, and providing the kind of "unassailable" data that will get the attention of a big partner. (And a lot of potential partners; in fact, let the bidding war begin...). The Zhao/Liu article, Pestell's work, CreatvBios comprehensive documentation of chemokines and PD-L1 and CAMLs and ctDNA... I foresee not only great ORR and OS data in the mCRC trial, and cures/long-term survival with an ICI, but a CCL3/4 biomarker to make it easy for clinicians to use. Oncologists are going to love this drug! Medicare will too. It looks like it's going to be a long, hot summer... and sometimes I wish I could go to bed tonight and wake up to ESMO in October... But I do trust this long, laborious process. It's kinda the way science and the medical profession works. Hang in there everybody.
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