Postet on Yahoo's TCLN board 05/22/99 by Ownotshort

There are many factors effecting the ability of Cotara to penetrate solid tumors. In theory TNT can target most any tumor because necrosis is a common characteristic of tumors. To understand how Cotara works, one must first take a short course in tumor biology. Dr. Rakesh Jane(sp?), from Harvard has published extensive papers on the structure of tumors. I believe his work was a spin off of Dr. Folkman's antiangiogensis research (as is Dr. Thorpe's VTA research).

In the simplest terms, all tumors the size of a pea have the ability to hijack the body's mechanism for growing blood vessels (angiogensis). This is why tumors grow. The problem (thankfully) is that they are not very good at angiogensis. They build very poor blood networks. Therefore, as the tumor grows, the cells that are further from the active growth area are slowly chocked off of their blood supply. Losing the blood supply kills the tumor cells. This gives you necrosis.

Now you know how the necrosis is formed. Lets move to targeting TNT to the tumor. The ultimate goal of TNT targeting is to get within 300 cell layers of all parts of the tumor. If we can get within 300 cell layers the radiation will kill it. This is where the challange is. Since there is a bad blood supply, TNT cannot get to all areas of the tumor, thus limiting its effectivness. This is where Dr. Epstein pulls out the big guns. He developed the Vasopermaetion Enhancement technology.

All of TCLN technologies are desigined to work together as one powerful cancer treatment. Now, the idea is to pretreat the tumor with the VE technology. The VE technology is simply TNT with a vasoactive compound. There are many vasoactive compounds IL-2,TNF and others. (TCLN has infact developed a compound that is genettically engineered to isolate the vasoactive region of the IL-2 molecule.) These vasoactive compounds cause blood vessels and their walls (endothelial cells) to open up, letting more blood to flow through to the tumor cells. The literature states there is a 2-3 hour window of increased permiability. This is your window to inject the TNT/radioactive isotope compound. The more TNT that can bind to the deeper parts of the tumor, the more your going to see the tumor shrink.

Therefore, TNT is limited by its ability to access the necrotic regions of the tumor. You wouldn't expect to see TNT have a lot of efficacy with a tumor that has a poor blood network or does not have a lot of necrosis.

A poor blood network is the real hinderance to all caner treatments. It effects chemotherapy and immunotherapies more than TNT. This is not necessarily do to the TNT antibody, but the radioactive isotope. The radioactive isotope can kill cells in a 300 cell radius. The gamma rays emmitted by the isotope damage the DNA, thus killing the cell and its ability to replicate. Since cancer cells are already weak, they are easier to kill than healthy cells (healthy cells can withstand more gamma ray hits on the DNA than cancer cells).

For a chemotherapy drug to work, the compound must come in direct contact with the cancer cell to kill it. Therefore, the problem of poor blood supply makes it very difficult for a chemotherapy drug to kill tumors. Radioactivity is just a more efficient killer than a drug compound.

Until we can overcome the blood supply issue, radioactive isotopes may become the best type of therapy. There are several coming to the market.
How can you beat the blood supply problem, thats the question?

Guess what, Dr. Thorpe may have found the answer. You gotta love it, TCLN acquired this technology for $25 million.

In the simplest terms, the Vascular Targeting Agent technology eliminates this issue altogether, in theory. The VTA technology in effect attempts to make the poor blood supply issue worse. The premise is since cancer cells die when they lose their blood supply (as evidenced by the existence of tumor necrosis), cutting off the blood supply may be the best means of killing the tumor. If you can cut off the blood supply at the outside edges of the tumor, all cells below will die. Therefore, tumor mass penetration is not a problem, its a benefit.

The VTA technology grew out of the antiangiogensis research field. The antiangiogensis inhibitors attempt to stop the cancer cell's ability to hijack the body's ability to build blood vessels. If a tumor cannot grow blood vessels, it cannot grow. In theory, you could keep the patient alive as long as s/he is taking the drug. The research around angiogenisis identified the factors that cause these cells to grow. VEGF (Vascular Endothelial Grow Factor) is the most well known of these factors.

Dr. Thorpe's idea was to use an antibody (or other compound) to target a factor that starts the blood clotting cascade specifically to the tumor vessels. The antibody side is the targeting side. Dr. Thorpe has developed antibodies that target antigens that exist only on cancerous endothelial cells within the tumor. He then attaches a factor that when it comes in direct contact with the endothelial cell it starts the blood clotting cascade. The blood clotting cascade is a self amplifying process. Therefore, a minute amount of drug can start a cascade that can block the whole blood vessel, killing all cells downstream of it.

In summary, Dr. Thorpe has developed a technology that has the ability create blood clots selectively within, and only within, tumor blood vesels.

Radioactive isotopes are millions of times more efficient killers than chemotherapy drugs, and blood clots are m(b)illions more efficient killers than radioactive isotopes. I think we've got cancer on the run now.

Now lets tie all of TCLN's technologies together to give you the big picture.

TNT is the most advanced of TCLN's solid tumor cancer products. TNT has the ability to target any cancer that has necrosis (most if not all cancers). TNT carries a radioactive isotpe to the tumor site, which then kills all tumor cells within a 300 cell radius. Each successive treatment creates more necrosis, thus more targets for the TNT anibody.

Eventhough TNT can target necrotic tissue, which exists in all solid tumor cancers, tumors have structural barriers (poor blood supplies)which may limit the effectivness of the treatment in some cancers (cancer specific and/or patient tumor specific). The VE technology was designed to help TNT overcome the blood supply problem. VE's are used as a pretreatment for the TNT therapeutic dose. For 2-3 hours after the administration of VE, there will be an increase in the blood supply to the tumor and related cancer cells. During this "window" TNT with its radioactive isotope would be administered. The result should be greater uptake of the therapeutic dose, thus giving greater efficacy. VE's are about 1-3 years behind TNT.

VTA's choke off the tumor's blood supply altogether, causing massive necrosis. Although VTA's should be very effective, they will have their limitations (not being able to kill off a layer of cancers cells that get their blood supply from outside the tumor mass by seepage at the perifery of the tumor mass).

The massive amounts of necrosis created by VTA's make a perfect target for TNT. TNT could then be used to kill all remaining cancers cells at the perifery of the tumor. This one-two punch, could be the death of many, if not most, cancers.

Wow! These are some very innovative technologies that all work synergistically to kill solid tumor cancers. They are all owned by TCLN.