Yes, the catch-22 mentioned in the article is that the clinical studies are done on late stage patients with usually at that point severely damaged immune system which of course wouldn’t produce desired effect especially if it is about using virus to cause flooding of the tumor with the immune response cells and not about virus directly attacking cancer cells. Also in the metastatic late stage one can imagine it isn’t really possible to inject each tumor.

This is a big simplification.

1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system.

2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness.

3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway.

4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors.

5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival.

This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.

I agree that it's a simplified explanation. However, in your first point you are making my point. An oncolytic virus can potentially give you a double whammy since even if the virus isn't able to kill a cancer cell, it might be able to recruit a local immune response and polarize cells from type 2 to type 1 immune response.

There are always exceptions to everything in biology, but the general mechanism of most chemotherapy drugs is that they preferentially kill or stall rapidly growing cells. That's why hair often falls out and you get skin issues. My point is that a successful immune response often involves rapid division of immune cell populations as well, which is dampened by chemo. You are also ineligible for many clinical trials if your blood cell counts get below a certain level.

Yes DNA-damaging chemotherapy drugs can induce p53, but many cancers inhibit p53 anyway. I'm not sure you would want to trade a general induction in p53 for losing a huge portion of your overall T-cell count right before injecting yourself with an oncolytic virus (depending on the tumor type).

You raise a number of good points, and there are a lot of subtleties including regulatory T-cells, which you mentioned. However, if you have the expertise and the means to design a custom treatment/regimen for yourself, I think that you can potentially do a lot better than just going through the meat-grinder of clinical oncology where the first line treatments are years behind cutting edge academic work. This paper supports this idea. I am not recommending that everyone who has cancer forgoes chemotherapy in favor of trying something risky, but as you said every individual case is different and it should be your decision whether you want to try a high-risk high-reward strategy or whether you want to go through multiple rounds of non-curative treatments which only slow down the inevitable and gradually sap away your strength and immune function. Especially if you have enough expertise in a relevant subject matter.

For example, my mother was diagnosed with stage 4 of a rare HPV+ squamous cell cancer. She was an expert on co-stimulation and immune tolerance, since she that is what she studied in the lab (https://tts.org/74-ixa/889-ixa-in-memoriam-agnes-marie-azimz... ). At times she was educating her doctor on co-stimulatory mechanisms, since he barely knew enough answer her questions and he would say the same types of things that you are saying: "it's complicated" "it might help clear cancer cells" etc..

There are a lot of customized treatments that she envisioned trying using her extensive expertise, and probably could have done so with the reagents in the lab or with her colleagues' help. Ultimately, she decided to trust the medical system but she did not respond to any chemotherapy. The one session which led to a reduction of tumor growth also led to a reduction in her blood cell counts (it was FOLFIRI), so the chemo had to be stopped. After that, she enrolled in an experimental cell therapy but it didn't work. Of course, the chances of it working are a lot less when her strength, general health, and immune function were already diminished.

It's one thing to talk about the complexities and the ethical risks of trying an experimental therapy, but when it happens to you or a loved one, the cost of failure is a lot higher and you might rethink your risk appetite. I am talking specifically about rare versions of tumors where the prognosis is poor.

In general, I don't even understand the point of making doctors go through all of the training they do, if they are forced to just follow the cookie cutter guidelines, which are influenced by the established drug companies.

If you had to give a percent figure, what do you believe your mother's chances were of discovering a radical curative treatment for SCC and curing her own cancer?

I have no way to give a percent figure. 1%? But it doesn't matter, since there is a known 0% survival rate using the known treatments for SSC. In those cases it should be the patient's choice if they want a slow painful slide or if they want to roll the dice with something well considered but less well tested before the chemo wears them down to the point where their strength and immune system are worn down from multiple rounds of chemo. Effectively, the right to donate your body to science.