Texmelanomex “Update”

Thanks Mike – am hoping for the day that you make it to NED or something similar and will be taking “mental break” too! 🙂 Until then keep fighting “the beast” – and also the spammers too!

good luck Mark

Thanks for the update! been wondering how he was doing.

Missy

That is good to hear. Thank you!

That is excellent news for Tex, Mike! Thanks for the update. The combo (PV-1+ Pembro) seems to be effective in a much larger set of patients than the Pembro alone (only 20% or so). That's to be expected since the Pembro can only help if one of the problems is that the immune system is being overly downregulated by PD-1 or programmed cell death protein 1 –see https://en.wikipedia.org/wiki/Programmed_cell_death_protein_1). Of course, PV-10 is limited to patients with injectable lesions or tumors, but it can train the immune system to immunize the body against any cells that share the same mutant antigens (cell markers) with those that it has been injected into.

The big problem is, of course, that the cancer patient’s immune system is not identifying that the cancer cells are enemy cells and thus does not attempt to destroy them (otherwise, . Only those cancers cells that are able to cloak themselves or evade the immune system in some way can survive in a patient with a normal immune system that is not being down-regulated by one of the body’s various immune system checkpoint mechanisms (that serve to prevent auto-immune disorders when normal cells come under immune system attack).

PV-10’s MOA (method of action) studies performed by Moffitt Cancer Center researchers find that PV-10 molecules invade the cell walls of cancer cells because of the unique properties of PV-10 and the acidic micro-environment of cancer cells. Normal cells are unaffected. Once inside the cancer cells, the cell begins to “lyse” and the cell bursts open.

Many other injectable substances can kill cancer cells but PV-10 is unique in 2 important ways.

One, it is safe and non-toxic to normal cells and has a half-life of about 30 minutes (except that portion which has entered the walls of cancer cells). It is excreted into the bile by the liver.

Two, after lysis, where the cell walls have burst open, killing the cancer cell, the cancer cell neoantigens (which may have been hidden previously) are preserved intact and not denatured as they are by other cancer killing agents (which are generally unsafe for normal cells.) This allows the immune system to produce specific antibodies for any newly discovered antigens thereby creating a vaccine effect for any additional cells with an identical neoantigen.

I am using the term neoantigen for antigens that are “new” that is, they are unique to cancer cells and not present in normal cells which have antigens that are known to the immune system as being “self”-antigens – those markers that allow a cell to prove it’s not an invader or a mutant. Neoantigens are those antigens that are not on the “safe” or “self” list.

Cancer cells, by definition, are mutated and over time they continue to mutate and thus the neoantigens by which the body identifies them can change as well. The more unique mutated cancer cells that are lysed and release intact their neoantigens, the better the chance that all of the various mutations of cancer cells can be detected and attacked.

This is why current PV-10 protocols allow for treating and retreating lesions until there are none that can be injected. The idea is both to reduce the tumor burden directly and attempt to release as many of the neoantigens (cancer markers that can be used by T-cells) as possible so that all of the many cancer cell mutations can be identified and killed by the immune system. It’s a Darwinian scenario for the cancer cells. By definition, only those that survive can multiply (and potentially continue to mutate). The purpose of Pembro at this point is to allow the immune system to be more aggressive (literally uninhibited), making more likely that cancers cells with the now-known neoantigens will be targeted and killed. The doctors must monitor side effects so they can limit the cytokine storms that can result from Pembro and other checkpoint inhibitors.