Checkpoint Inhibitors and Covid 19
Could the coronavirus be a greater threat to cancer patients undergoing immunotherapy, or could it actually highlight new cancer breakthrough opportunities ?
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About this content
This page content originates from a conversation among patients.
Does this conversation highlight something relevant, both in terms of patient understanding and patient decision making, or could it highlight something even greater in the search for new breakthroughs.
At no time does this conversation attempt to solve, it does however highlight.
WHAT | PROBLEM | ANSWER [1/3]
Patient Observation and post-
“Interesting article about COVID 19 and immunotherapy check point inhibitors. Does this mean a PDL-1 negative person won’t get the cytokine storm?”
Controversies about COVID-19 and anticancer treatment with immune checkpoint inhibitors
by Melissa Bersanell
Source = Future Medicine
WHAT | OBSERVATIONS | ANSWER [2/3]
“I’ve often wondered if those of us who had a positive response to checkpoint inhibitors like Keytruda, had an overall stronger immune system as a result and were less likely to become ill – this seems to suggest so. Very interesting!”
” What is the cytokine storm?”
“I wonder if cells expressing PDL-1 can be unlocked by ICI, the same way the protein on the covid virus unlocks the healthy cells in this case and destroys them. If one does not express PDL-1 and if ketruda would be locked out, is it possible that those PDL-1 negative people would also be resistant to the virus protein that causes the cytokine storm.”
WHAT | PROBLEM | EXPLANATIONS [3/3]
Immunotherapy’s fix for HER 2
RE Stronger Immuniity response patients
“I agree, as I believe a lot of the trial patients may not mount a sufficient response. So even when the T Cells make a successful entry into the mutated cell, due to the Keytruda intervention, they do not do so in sufficient numbers, and are quickly overwhelmed and weakened. This maybe why we see many partial but not full responses.
Scientists know this, and that many immune responses, simply do not produce T Cells in sufficient numbers to overwhelm and destroy the cancer.”
RE Unlocking the PD-L1
“Hi – I am not sure if I follow correctly, but hopefully this helps.
“RE PD-L1 Unlocked” –
- If a mutated cell has a high percentage of ligand expression on its surface, then this can be strong evidence of how a mutated cancer cell is able to evade the immune systems lymphocyte response. So if the percentage of PD-L1 is low or absent, then it is less likely that the PD-1/PD-L1 is a factor.
- After the Covid 19 pathogen has been successful in lodging in the larynx & throat, it then binds with “Ace-2 receptors” to which it is a good match. It is then able to insert its snippet of RNA Code and capitalise off our bodies cellar communication, and enter new host cells, where they can grow and divide successfully.
- The Checkpoint pathway is de cloaking the cell, whereas Covid 19 is an invasive action into the cell. 2 very different mechanisms.
- What you refer to in the unlocking is more aligned to a different type of immuno-monoclonal antibody pathway such as egfr pathway, where the cancer cell surface has receptors (ie FGFR2) who receive, much like the throats Ace-2 receptors.
- Currently if you follow the science success is gaining momentum with sophisticated monoclonal antibodies that attach to the receptors and block growth signal ( instructions) from entering the cell.
- Re Keytruda –
Keytruda has no interaction with a cancer cell. It’s primary function is to attach and block the T Cells PD-1 checkpoint, rendering it redundant and unable to bind with any PD-L1’s.
- When a T-Cell approaches a mutant Cancer with PD-L1 expression, it is already primed and activated for attack, it is simply the presence of the pd-l1 and it’s successful binding that disarms the TCell attack – so when pd-1 is blocked by Keytruda, then the attack continues.
- It is unlikely that a T cell will approach a cell expressing pd-l1 if it is genuinely healthy.
Re Cytokine Storm.
- “Like the throat, the lungs have an abundance of rich cells with Ace-2 receptors on their surface, and in SOME cases the pathogen can migrate down the respiratory tract into the lungs.
- If this activity occurs then many cells will be destroyed and the lungs begin to congest from the dead and broken cell residues. The patient will then need an ICU intervention.
- This congestion issue is the most likely outcome and is in a small percentage of those infected. This activity will obviously impact people with predisposed lung / heart issues – those without underlying issues will recover with intervention.
- This is the response in the majority of cases and is not a cytokine storm
Cytokine storms are in a nutshell an overreaction of the T cell response and creates an inflammatory environment that in a very small percentage, will succumb to.
This is a less likely outcome, even as we see the dire outcomes mount.
The basic and common thinking is, that people with weakened immune systems are the ones who get cancer. This is fundamentally incorrect- yes during treatment cancer patients immune systems are substantially weakened and we do become very exposed.
Yes viruses and cancers are in someways similar. Could science find a way into a cell via receptors ? yes, this is what is being worked on atm, specifically CAR T Cell.
The Covid 19 is milder than most others, which is partly the reason for its success in spreading, but it is far less the killer compared to it’s predecessors which kill at a much higher rate.
It is likely that it will be in our population for many years to come and that the most impacted will more likely be those with lung and heart issues. It doesn’t appear that cancer patients are significantly more at risk.”
human epidermal growth factor receptor 2
Source – NCI
A protein involved in normal cell growth. Human epidermal growth factor receptor 2 may be made in larger than normal amounts by some types of cancer cells, including breast, ovarian, bladder, pancreatic, and stomach cancers. This may cause cancer cells to grow more quickly and spread to other parts of the body. Checking the amount of human epidermal growth factor receptor 2 on some types of cancer cells may help plan treatment. Also called c-erbB-2, HER2, HER2/neu, and human EGF receptor 2.