Some quotes of comments from Quora regarding the cancer 'vaccine' study:
Using a checkpoint inhibitor like anti-OX40, the CD4 T-cells can be activated to attack the cancer and in turn those cells can migrate to the rest of the body to attack metastases.
What exactly are the limits? For one, the FDA seems to hate vaccine adjuvants especially CpG DNA...
In this study, they required local stimulation of the tumor microenvironment with CpG DNA. For certain cancers, it’s fairly trivial to reach the microenvironment but it will be much more questionable for difficult to reach cancers like brain or lung cancer.
We also know from a lot of experience with immunotherapies that tumor response tends to be extremely heterogeneous. For these studies, they used various cancer cell lines and injected them into the mice. However, since these cells are fairly clonal, it wouldn’t be a surprised that the T-Cells would generate a widespread response. I’m curious how this would look like for a more representative humanized-xenograph mouse model. A more heterogeneous tumor may provide a drastically different result in gaining a strong immune response. Again, this is a limitation that Levy’s team is well aware of and it sounds like they are already working on the next wave of studies.
As an aside, this is barely a “vaccine”. It’s probably better described as an coupled immunotherapy. I’m curious how a bispecific or a conjugated OX40 will behave.
In summary, this is a very well designed proof of concept study backed by strong scientific insight and a sound mechanism of action. However, a lot of the moving parts aren’t very feasible in the clinical setting notably the use of a microinjection along with the use of vaccine adjuvants. That said, these are fairly fixable problems and should be resolved through drug development.
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Here are some thoughts…the team used an agonist…one more time…agonist…the studies that I know of that involved agonists..did not go well.
Upregulating T cells, using an agonist…two critical goals..activation of the T cell and downstream B cell activation ..memory
Lets go back to 1999…jesse geisinger..disease caused by genetic variant …he agreed to undergo gene therapy with weakened -cold-adenovirus…and sadly died. His immune system was turned on….then could not turn it off….
It worth noting in the section of Letter from Chairman and CEO, PAB Business Review 2018 it mentions that "PAT-DX1 has potential as a therapy for cancers that remain difficult to treat including glioblastoma, endometrial, ovarian, pancreatic, colon and some breast cancers. To date, PAT-DX1 has performed particularly well in animal models of glioblastoma."
PAB Price at posting:
4.1¢ Sentiment: Buy Disclosure: Held
