My Immune Therapy Plan

Contact: Marc Perkel marc@perkel.com

Nivolumab (Opdivo) and other immunotherapy drugs work by both boosting the immune system and targeting cancer using "checkpoint inhibitors". Some cancers put put a substance called PD-L1 that makes the adaptive immune system (T Cells) not be able to see the cancer. PD-L1 is an "I'm a friend - don't kill me" signal that hides the cancer from attack. Opdivo removes the mask allowing the immune system to see the cancer and attack it. In some cases even leading to a complete cure. This is part of my Immune Strategy plan for cancer .

However ...

You can't unmask something that isn't masked in the first place so if you have PD-L1 then that's great. But I don't have it so a drug that removes a mask that isn't there isn't likely to work for me.

Nivolumab apparently does more that just remove the mask. Although the literature focuses on PD-L1, the list of possible side effects look similar to people who have autoimmune problems. In other words - it looks like it also stimulates the immune system to the point where it might attack your body's good cells. It appears that Nivolumab has more than one function - to unmask the cancer - and to stimulate the immune system and put it in learn mode so that the T cells can identify the cancer and attack it.

The Abscopal Effect

The Abscopal Effect is something that has been observed but, in my opinion, not got the attention it deserves. In some patients receiving radiation therapy, and often in combination with immunotherapy, the radiation kills cancer cells in a way that exposed the antigens (something that the adaptive immune system sees to identify cancer) to the T-cells, and causing the T cells to learn the cancer and attack it all over the body, not just where it was treated with radiation. This effect happens rarely and it is believed to be the result of a combination of events timed right to cause the immune system to "go to school" and learn the cancer's antigens. And it is this effect that I'm going to try to take advantage of to beat an unbeatable cancer.

The bast way to understand Abscopal effect is that you are making a vaccine in your body that immunizes you against your own cancer. And if you succeed then the immune system kills off all the cancer and you're now cured from that particular cancer. So the goal is to try to do something to trigger this effect.

It seems to me that even without PD-L1 - if the radiation can expose the cancer's antigens to the T-Cells, then radiation substitutes for PD-L1 unmasking allowing other properties of Nivolumab to go to work creating the immune response that makes Nivolumab work. But to do this, I have to get the sequence and timing right. And that is of course - the tricky part, I'm not a doctor - and I need to figure out stuff the doctors haven't yet figured out.

Important Assumptions in triggering the Abscopal Effect

I'll start with a list of what I know - or what I think I know.

The Abscopal Effect has the potential to take me to long life and possibly a total cure if it is successful.

In order to be successful the cancer's antigens have to be exposed and the T Cells have to make contact and learn the cancer's antigens. So exposure of the antigens and the schooling of the immune system have to happen at the same time. There has to be contact and interaction and the adaptive immune system has to be as ready as possible. So anything that exposes the antigens better, enhances adaptive immune response, and assures contact between the immune system and cancer antigens are all good things and the sequence and timing is critical.

Cancer is not just one organism so if I kill only some of the cancers then the immune system might not learn all of them. Things like radiation have the advantage that they kill everything, where a targeted therapy might not create as diverse a sample. One wants to present the T cells with a buffet.

This only has to be successful one time to work. Once the immune system learns the cancer the battle is won. So the possibility of several attempts trying different things is worth considering because once you get it right then I win, permanently. So trying different immunotherapy drugs in combination with different kind of radiation treatments can be attempted until one works. But once you succeed - it's like creating a cancer vaccine in my body - and it's permanent. It will kill all cancer everywhere and keep those cancers from coming back. So I only have to be right once.

Rarely does a radiation treatment just happen to lead to the Abscopal Effect. Nor does the mere combination of immunotherapy and radiation. The cases out there that document this mostly involve people getting lucky, where lucky means that I need to understand the luck in a way that I get lucky too. Clearly timing is important. Probably the way the radiation is given is important. Definitely wouldn't want to take any immuno suppressants that would stop the immune system from learning. One has to create a "classroom" where the student and the teacher are there at the same time and are ready to learn.

Since no one knows the right answer to many variables that will affect success, maybe the right approach is to try them all. For example, you hit the tumor(s) with different kinds of radiation, different strengths, different patterns, with the idea that you aren't trying to kill the tumor with radiation. You don't want to burn up the tumor in a way that destroys the antigens. You want good contact between dead tumor and T cells, of mortally wounding them in a way that leads to apoptosis is what we need to do. Giving the immuno drugs shortly before the radiation so that they are at their peek when the radiation occurs. And if one drug doesn't work we try the same thing again with a different drug. So if I don't know the right combination I try them all till I get lucky.

Radiation or Cryotherapy?

In addition to radiation there is also an option for cryotherapy, which is freezing the tumor instead of burning it. There is information that freezing could work as well and perhaps I can try both. If one doesn't work make the other will. Just more things to try.

Radiation would attack the center of the tumor where cryotherapy would attack the tumor surface. I don't know which is better but the idea that they are different adds to the possibility that if one doesn't work the other will.

Or - even better - maybe I should do both radiation and cryo at the same time? I take immuno drug(s) and do both and if any of this works then I win. Something I'm going to ask about.

Abscopal Effect vs. Checkpoint Inhibitors like PD-L1

Since I don't have any PD-L1 the checkpoint inhibitor part won't do anything for me. But I'm thinking radiation and/or cryo will work even better. Why? Because in PD-L1 cancers maybe only some of the cancer expresses PD-L1 so unmasking the cancer with a checkpoint inhibitor doesn't expose the antigens of all the cancer. So I would be back to playing genetic whack-a-mole. What I need it to attack all my cancer mutations at once. Radiation and cryo kill all the cancers and exposes all the antigens to the adaptive immune system making it possible to create an immunity to all of it and get a complete response.

Thoughts on Radiation Treatment Strategy

It's not just getting the radiation but it matter how the radiation is applied. I think it's important not to try to kill or severely damage the tumor, but rather to kill a small piece in the middle if the tumor using a cone shaped pattern. That will provide dead tumor in the middle with a variety of dying and wounded tumor down stream. but next to live tumor so that there's good blood contact with the irradiated tumor areas.

I'm also thinking that maybe 5 treatments to minimize collateral damage and not train the immune system to kill good lung cells, which I suppose could happen. And a fractionated plan would spread the radiation out over a longer time so if there's a timing sweet spot I'm moe likely to hit it.

Making it happen

Still gathering information. The more you know the luckier you get. First step is to get my oncologist on board and excited about the plan. I have a great oncologist and I think he will be willing to go along with anything that makes sense and isn't too far outside of normal cancer treatment. Especially if I'm asking for normal things that they already do. It looks like this all can be done with "off the shelf" procedures using drugs and technology they use all the time already.

I need to talk to a radiologist about a "custom" treatment based on the goal of exposing cancer antigens and not burning out the tumor. Burning out the tumor is worse because that much radiation tends to suppress the immune system and cause collateral damage in normal tissue. My thinking is to focus on the very center of the tumor so that the peripheral damage is still within the tumor. The idea is that different parts of the tumor would be exposed to different amounts of radiation and as long as some part of the tumor is the "sweet spot" then the T Cells will be able to get at it and learn the cancer(s) I have.

I need to talk to an immunologist as well to find out what I can do before hand to put my immune system in a ready state. This might be everything from eating my vegetables, getting an extra flu shot and pneumonia vaccine to piss off my immune system, and various other immune stimulants including Nivolumab or drugs to treat other ailments to get the T cells primed for the encounter. I suppose anything that has a side effect warning if possible autoimmune complications is likely to be what I'm looking for,

Once I have a complete plan then the idea is to go for it and see if I get lucky.

It's a long shot

While this idea seems brilliant, and might even be brilliant, that doesn't mean it's going to work for me, even if it is the right idea. My current prognoses, especially someone without PD-L1 is nearly 100% fatal and to beat that when I'm not a doctor and have avoided the "gooey sciences" - this is generous to even calling it a long shot. So the reader should assume that this is still going to kill me eventually, and if I do make it that will be an unexpected pleasant surprise. I know I seem to people like I'm a super hero, but most of what I do is just that I'm more persistent and I'm unrestrained by conventional thinking. An I have technical skills that are beyond the scope of learning of most other people.