Bavituximab History -
Phosphatidylserine, "PS", is a molecule that normally lines the inside layer of our cell walls, and is not normally found on the outside of our healthy cells.
Dr. Philip Thorpe and Dr. Sophia Ran found that due to the stressful tumor environment, the cells that make up the blood vessels of tumors expose PS on the outside of the cell. Normal blood vessel cells do not expose PS, just tumor vessels.
They hypothesized that if they could design an antibody that stuck to PS, and if they could attach some sort of molecule to the antibody that would kill a cell, they could have a potent targeted therapy with potential for treating any tumor, avoiding healthy tissue and only killing the tumor blood vessels, thus starving/killing the tumor, (a type of drug now typically called a VTA, or VDA, Vascular Targeting Agent, or Vascular Disrupting Agent).
As a first step, their team designed an antibody to stick to PS. It didn't have any extra cell-killer molecule attached to it yet. They just wanted to see, as a first step, if the antibody simply got to where it was supposed to go, and stuck to the exposed PS.
It did.
But they were also very surprised at what else happened....
The plain ("naked") PS-targeting antibody appeared to alter the whole immune response to the tumor! Immune cells flooded in, in great numbers, and dismantled/destroyed the tumor blood vessels.
It was a big surprise....
(The prevailing assumption/understanding of the time was that PS is "immune-neutral", that it neither invokes an inflammatory or an anti-inflammatory response from the immune system.)
Around the same time, in other labs around the world, other scientists were making fundamental discoveries into the nature of PS itself, while studying a relatively newly discovered process named apoptosis. In all multicellular organisms, a dying cell poses a threat to it's neighboring cells. If the dying cells is not cleared away promptly, it can leak dangerous chemicals which can then threaten the nearby cells, (which doesn't bode well for THEIR neighboring cells, etc.). You can quickly understand, that for the success of multicellular organisms, a process evolved for cells to show externally that they were dying, so they could be promptly disposed of by the immune system. (Sort of a "cellular suicide" for the greater good of the whole). A universal early sign/"signal" of this process was discovered - the PS in the cell wall flips to the outside of the cell. Exposed PS on cells is an early and pervasive sign that a cell is dying a natural death.
It soon became clear that the prevailing understanding that PS is "immune-neutral", was flat-out wrong. It turns out that PS is actively anti-inflammatory. Exposed PS tickles certain receptors on immune cells that cause those cells to behave very differently than if they had met an invading virus or other foreign critter that needed to be fought and destroyed. When the immune cells meet up with exposed PS, those immune cells go into a kinder gentler clean-up mode, and, unlike the "memory" immune response to some foreign invaders, after meeting PS, immune cells do NOT make a note of what they're cleaning up to stay on guard for it in the future.
(Later, in future posts, I'll provide examples as to how, (and how many!), disease states, and foreign invaders, have evolved to exploit this specific crucial "fork in the road" in our immune system's rulebook)...
Stay with me...
So, the big surprise of Dr. Thorpe's & Dr. Ran's naked antibody that stuck to PS, (Bavituximab), having such a robust effect against tumors in that first experiment, turmed out to be due in part to the fact that the Bavituximab was simply covering the PS, not allowing the PS to tickle the receptors on the 'first-responder' immune cells that would have sent signals to all subsequent arriving immune cells to "take it easy". With the PS covered, the arriving immune cells, and hence the subsequent arriving immune cells, then attacked the tumor vessel cells with vigor, as if they knew it was something that needed to be destroyed.
In a nutshell-
It turns out Bavituximab goes to the right spots, (since PS is only exposed on tumor blood vessels and not healthy vessels), AND, once it's there, in all the right spots, covering the PS, it alters the immune response, 'allowing' the immune system to "see" the cancer as something that needs to be fought more strongly and effectively.
That was just the beginning of Thorpe and Ran's discoveries...
It also turns out that all enveloped viruses (HIV, HCV, flu, ebola, RSV, VSV, and a few dozen others), as well as virally-infected cells, also "wear" exposed PS on their coats/envelopes. When these viruses are born, (from one of our own cells), they take a bit of the cell wall as their own coat. They wind up having PS exposed on themselves.
and that's not all-
(more to come on several parasitic and other diseases).
Is this all some Sci-Fi Pie in the Sky?..
Consider these things-
* All the data to date, (both pre-clinical, and now human data),
* and the growing number, and quality, of researchers now involved.
* Pre-clinical data:
Bavituximab showed efficacy, with perfect safety and no toxicity against Breast tumors, Prostate tumors, Brain tumors
as well as efficacy against metastatic tumor growth (which is usually responsible for killing the cancer sufferer).
Bavituximab also stuck to every enveloped virus - and virally infected cell - it was experimented with, (including HIV, H5N1, and over a dozen others, actually every enveloped virus they tried), and Bavituximab showed efficacy in animals against a fatal hemorrhagic virus, HCV, VSV, RSV.
* The human clinical data to date has also shown efficacy and perfect safety against multiple tumor types, as well as HCV.
* The people who are conducting research work with Bavituximab. Where is bavituximab being experimented with?
Bavituximab, (and it's inventor Dr. Thorpe) is a part of the Bill Gates Foundation's Collaboration for AIDS/HIV Vaccine Discovery, - CAVD.
Bavituximab is also being researched by the Director of immunology at Duke University, who is also the Director of CHAVI (Center for HIV/AIDS Vaccine Initiative) to see if it is effective in helping the immune system fight HIV infection.
Bavituximab is also at Harvard for HIV research.
Bavituximab is at MD Anderson in a cancer clinical trial for any solid tumor.
Bavituximab is at Johns Hopkins Medical Center in a clinical trial in patients with HIV, and hepatitis C.
Bavituximab is in a bio-safety level 4 lab in Galveston Texas for investigative work into it's possible effects against HFV's - (Ebola, Marburg, etc.)
Bavituximab research has received three separate government (DOD) grants for : Hemorrhagic fever virus research, prostate cancer research, and breast cancer research.
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