Twinter, Ken, Misiu--Appreciate the back and forth on the trial and how we might expect things to turn out. I do believe there is one variable at play that might influence results in the 350mg arm of the trial that hasn't been discussed. And that is the possible influence of mRNA vaccines on PDL-1 expression. To whit:
"Research indicates mRNA vaccines act as potent immune modulators, stimulating a surge in type1 interferon that primes the system to better recognize and attack tumor cells, especially in "immune-cold" tumors that usually don't respond well to ICIs." (The quote is from google ai, and lines up with the details in the Grippen article in the Oct 2025 issue of Nature. Grippen's study suggested a doubling of overall survival in NSCLC and melanoma, so the influence is significant... if the retrospective study holds up.)
Will 350mg of leronlimab PLUS an mRNA vaccine boost PDL-1 levels enough to qualify for an ICI? That is one of the questions this trial will answer, whether or not we asked it... or wanted to! And the answer might confuse things a bit. This is where all the documentation that Creatv Bio is doing will allow Cytodyn to track the biomarkers and parse out the individual contributions of each therapeutic. At least I hope so.
Personally, I am "holding out hope for those first few" because the combination of 350mg and an mRNA vaccine has never been specifically studied before, at least prospectively, in cancer. Who knows, the mRNA vaccine may have influenced the MASH trial results, which, as you recall, showed surprisingly effective results at the 350mg dose. (And that is rank speculation on my part... an alternative explanation to Ohms thoughts).
In terms of cancer therapeutics, I think we are in a post-mRNA world, so to speak. Basically, all the ICI trials since the mRNA vaccines need to be re-evaluated... (Or, they should be. And yet we haven't heard anything about this from the FDA or NIH. Which leaves me thinking--what the hell are they thinking?). And not a word from all the ICI manufacturers, whom I suspect aren't keen on dealing with these implications. And who knows, apparently the mRNA vaccine may help chemo work better, too. Could that be a reason I am cancer-free for 3.5 years after surgery, oxaliplatin and capecitabine, for locally advanced mss CRC? If I was an unknowing guinea pig... well, science works in mysterious ways.
It strikes me that the two most important therapeutic advances in cancer in the last couple years--boosting PDL-1 by leronlimab and the mRNA vaccines--were both accidents, essentially. That is one reason why I think AI might not be such a big deal in medicine--it can't replicate the plodding, mistake-filled process of science as a human endeavor. Where so many breakthroughs come from accidental observations, like most famously penicillin, but also x-rays, warafin, quinine, and the link between the pancreas and blood sugar levels/diabetes. But I digress...
The money question--will patients taking mRNA vaccines screw up the mCRC trial with leronlimab? Well, it will potentially help the PFS and OS numbers in the 700mg cohort, whether or not they receive an ICI. So no problem there. And it might help those in the 350mg cohort survive long enough to benefit from an ICI. Which will confuse the dosing issue. But if the results in the 700mg cohort are close to the numbers that have gotten us all excited--60% ORR in mCRC, without an ICI... 5 out of 5 alive after 5 years when paired with an ICI in mTNBC--then the influence of the mRNA vaccine will be seen for what it is--background noise, likely with a small, additive benefit. If it turns out the mRNA vaccines, paired with leronlimab, do provide a substantial benefit... well, leronlimab is still a huge part of the solution. Let's say it's the combination of mRNA vax and leronlimab that controls metastasis... it still means leronlimab has a crucial place in cancer treatment.
This is all educated speculation... because the efficacy of both leronlimab and mRNA vax in cancer treatment has been prospectively proved. We don't even know if or how the mRNA vaccines helped out our Ladies, in fact. I'm hopeful we'll get some complete responses in the 700mg arm--without an ICI. That would prove the efficacy of leronlimab added to SOC in mCRC, and establish an MOA independent of ICIs (by controlling metastasis). Further on down the line, they may very well need an ICI if they progress. Either way, leronlimab saves lives. And the documentation of all these biomarkers in the trial will provide the "unassailable evidence" we need to revolutionize cancer treatment in our time.
Look, I'm a carpenter and documentary artist, with absolutely no background in the hard sciences. My last lab class in biology was way back in high school! I do read quite a bit about leronlimab and CCR5 and biotech, though... but it is book knowledge, and my comments/conclusions may be off-base. So Kat, Ohm, Plot et al--and anyone with a medical background--please weigh in here. Especially on the implications of the mRNA vaccines on contemporary clinical trials in cancer. And, if you had cancer and didn't have access to leronlimab--would you take an mRNA vaccine along with an ICI, if it was prescribed... based on what you know from the Nature article?
Thanks again to Twinter, Ken and Misiu for getting the dialogue going and for interesting posts. And--would you all seek out an mRNA vax if you were getting an ICI for cancer?
Sherlock57 (from a cold, overcast, sad Minneapolis)
"Research indicates mRNA vaccines act as potent immune modulators, stimulating a surge in type1 interferon that primes the system to better recognize and attack tumor cells, especially in "immune-cold" tumors that usually don't respond well to ICIs." (The quote is from google ai, and lines up with the details in the Grippen article in the Oct 2025 issue of Nature. Grippen's study suggested a doubling of overall survival in NSCLC and melanoma, so the influence is significant... if the retrospective study holds up.)
Will 350mg of leronlimab PLUS an mRNA vaccine boost PDL-1 levels enough to qualify for an ICI? That is one of the questions this trial will answer, whether or not we asked it... or wanted to! And the answer might confuse things a bit. This is where all the documentation that Creatv Bio is doing will allow Cytodyn to track the biomarkers and parse out the individual contributions of each therapeutic. At least I hope so.
Personally, I am "holding out hope for those first few" because the combination of 350mg and an mRNA vaccine has never been specifically studied before, at least prospectively, in cancer. Who knows, the mRNA vaccine may have influenced the MASH trial results, which, as you recall, showed surprisingly effective results at the 350mg dose. (And that is rank speculation on my part... an alternative explanation to Ohms thoughts).
In terms of cancer therapeutics, I think we are in a post-mRNA world, so to speak. Basically, all the ICI trials since the mRNA vaccines need to be re-evaluated... (Or, they should be. And yet we haven't heard anything about this from the FDA or NIH. Which leaves me thinking--what the hell are they thinking?). And not a word from all the ICI manufacturers, whom I suspect aren't keen on dealing with these implications. And who knows, apparently the mRNA vaccine may help chemo work better, too. Could that be a reason I am cancer-free for 3.5 years after surgery, oxaliplatin and capecitabine, for locally advanced mss CRC? If I was an unknowing guinea pig... well, science works in mysterious ways.
It strikes me that the two most important therapeutic advances in cancer in the last couple years--boosting PDL-1 by leronlimab and the mRNA vaccines--were both accidents, essentially. That is one reason why I think AI might not be such a big deal in medicine--it can't replicate the plodding, mistake-filled process of science as a human endeavor. Where so many breakthroughs come from accidental observations, like most famously penicillin, but also x-rays, warafin, quinine, and the link between the pancreas and blood sugar levels/diabetes. But I digress...
The money question--will patients taking mRNA vaccines screw up the mCRC trial with leronlimab? Well, it will potentially help the PFS and OS numbers in the 700mg cohort, whether or not they receive an ICI. So no problem there. And it might help those in the 350mg cohort survive long enough to benefit from an ICI. Which will confuse the dosing issue. But if the results in the 700mg cohort are close to the numbers that have gotten us all excited--60% ORR in mCRC, without an ICI... 5 out of 5 alive after 5 years when paired with an ICI in mTNBC--then the influence of the mRNA vaccine will be seen for what it is--background noise, likely with a small, additive benefit. If it turns out the mRNA vaccines, paired with leronlimab, do provide a substantial benefit... well, leronlimab is still a huge part of the solution. Let's say it's the combination of mRNA vax and leronlimab that controls metastasis... it still means leronlimab has a crucial place in cancer treatment.
This is all educated speculation... because the efficacy of both leronlimab and mRNA vax in cancer treatment has been prospectively proved. We don't even know if or how the mRNA vaccines helped out our Ladies, in fact. I'm hopeful we'll get some complete responses in the 700mg arm--without an ICI. That would prove the efficacy of leronlimab added to SOC in mCRC, and establish an MOA independent of ICIs (by controlling metastasis). Further on down the line, they may very well need an ICI if they progress. Either way, leronlimab saves lives. And the documentation of all these biomarkers in the trial will provide the "unassailable evidence" we need to revolutionize cancer treatment in our time.
Look, I'm a carpenter and documentary artist, with absolutely no background in the hard sciences. My last lab class in biology was way back in high school! I do read quite a bit about leronlimab and CCR5 and biotech, though... but it is book knowledge, and my comments/conclusions may be off-base. So Kat, Ohm, Plot et al--and anyone with a medical background--please weigh in here. Especially on the implications of the mRNA vaccines on contemporary clinical trials in cancer. And, if you had cancer and didn't have access to leronlimab--would you take an mRNA vaccine along with an ICI, if it was prescribed... based on what you know from the Nature article?
Thanks again to Twinter, Ken and Misiu for getting the dialogue going and for interesting posts. And--would you all seek out an mRNA vax if you were getting an ICI for cancer?
Sherlock57 (from a cold, overcast, sad Minneapolis)
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