Doctors hail world first as woman’s advanced breast cancer is eradicated

cheers! DOIs really should be a required part the title here (if available)...

Thanks! That is an excellent and relatively modern review article.

My Mom was diagnosed with two kinds of stage III lymphoma just after Christmas last year. She started chemo a few months ago. Three treatments in, all of the tumors were no longer visible in a PET scan.

I'm still trying to emotionally accept that the nightmare is over. It seems almost too easy, like it's just setting us up to let us down. It can come back, of course. But she's in remission now and totally done with treatment.

Whenever I think of oncologists, I always imagine how much it must suck to tell people they have cancer every day. I'd never really considered the other side of that. To get to tell someone you have completely cured them of a disease that would surely have killed them. It must be an incredible feeling, like beating Death at his own game.

The unvarnished truth: Imagine going from "You have 3 years to live" to "You have no more cancer but old age will get you in the next 20 years."

Once we solve cancer, we will need to solve longevity, the greatest health problem in the world.

It is a spectacular proof of concept, but it's not exactly game-changing in any way that will revolutionize cancer care around the world in the near future. This was incredibly labor- and capital-intensive procedure that involved extracting tumor material, sequencing its genes, determining which main mutations appear in the material, finding immune cells that attack that specific mutation, replicating those immune cells, and then injecting them into the patient. Since most cancers carry unique or nearly-unique mutations, this treatment would need to be tailor-made for every single patient, meaning its use would only be limited to those with a lot of resources.

Let's be optimistic, but cancer is a very broad and difficult problem. Many treatments are overhyped by the press office of the hospital/university.

The article has a few good cautious warning, in particular:

> But experts caution that the treatment has only proved itself in one woman and that the clinical trials are needed to see how effective the therapy could be in other cancer patients.

Too good short explanations in comic forms are:

http://phdcomics.com/comics.php?f=1162

https://xkcd.com/931/

Its not game-changing. That said, its a great step forward.

The T-Cell treatments or CAR-T cell treatments is one of the most promising lines of research in cancer treatment. Fred Hutch is doing a lot of research on right now. Seattle Cancer Care (which is associated with Fred Hutch) has an entire floor devoted to CAR-T trials. https://www.seattletimes.com/pacific-nw-magazine/the-hutch-i...

The interesting bit is that this is a successful trial on a solid tumors. CAR-T has shown that its most effective on non-solid tumors or blood based cancers. A few months ago there was a Stanford press release on them doing a combination of injecting solid tumor CAR-T and alcohol, which caused a singular tumor to be attacked and removed.

Another good step forward. I am excited about the advances that are being made using things like poliovirus to attack lethal cancers.

There has been a ton of investment in the area of identifying tumor mutations and re-engineering patients own cells to fight the tumors. This is called "autologous cell therapy". Autologous meaning using a patients own cells and cell therapy meaning cells rather than small molecules or large molecules like proteins are the "ingredients" of the drug

The 1980s saw the introduction of proteins as therapies using genetically engineered organisms to make drugs. Previously drugs were either extracted and purified from natural sources of chemically synthesized. Only small molecules could be synthesized, not proteins, so the ability to make therapeutic proteins -- much larger and more complex than traditional small molecule drugs -- enabled a new class of drugs and companies like Genentech and Amgen

Cell therapies potentially represent another massive leap in ability to treat disease. There are a few genetically engineered cell therapies approved today, kymriah and yescarta. They are engineered to attack cells that express a molecule called CD19. This molecules is found mostly on B cells in the blood. So naturally these drugs are used for B cell lymphomas

It has proven difficult to make these cell therapies work in other cancers, especially solid tumors. Solid tumors are more difficult for immune cells to penetrate (denser and surrounded by a complex mass of fibroblasts, blood vessels and immune cells called the tumor micro environment), they have more defenses against immune attack, and they have fewer good molecules to target -- while CD19 is pretty specific to B cells and thus a good target, most solid tumor targets are either expressed on healthy tissue (so targeting these targets would attack healthy cells as well) or are not consistently expressed across cancers

The approach in this article represents an effort to solve the latter problem. There has been a lot of investment in this space by VCs and to a lesser extent pharma. There are basically two approaches, each with a set of delivery options:

Neoantigen targeted therapies: these aim to find novel tumor mutations and target them with drugs. The advantage here is that you'd have mutations specific to a tumor. The disadvantage is that you'd have to tailor each therapynto each patient which would be insanely expensive. There are many efforts to find shared neoantigens that could be used to treat a variety of patients, from what I've heard this isn't going super well. Neon therapeutics, gritstone oncology, moderna and several others are active here

Another approach is targeting "wild type" antigens (i.e. Not mutants) that are specific to cancer and not other tissues. Advantage is that you'd need less customized therapies. Some common shared tumor antigens people are focused on are NY-Eso-1, mage-A4 (or a3 or a1, don't recall). Several companies are in the clinic here but still not clear if the approach works. Aduro, immune design, biontech, moderna, neon, gritstone, 3t biosciences and others are involved

Delivery options are most commonly autologous cell therapy but this is super expensive and it is very hard to get consistent product. The manufacturing process itself contributes a ton of variability. Even using a different brand of the same type of flask can lead to a final product with vastly different biological function. Basically you draw cells from a patient, ship them to a lab, process them and ship them back. Nobody really knows if this process can scale to anything beyond just a few super rare cancers into something like say diabetes. Also the approved drugs to date have had major side effects which would prevent their use in any but the most devastating disease

Another approach is off the shelf allogeneic cell therapy. Here you just make cells that work in any patient. Immunogenicity is a potential concern

Others are using bacteria, viruses or non viral vectors to deliver mRNA encoding for the antigens to dendritic cells, which are cells that tell T cells which antigens to attack. Biontech is a leader here. This is sort of a "bounce shot" approach. If it works it would be amazing but it is very technically challenging and I don't really know if the exact details of the mechanism are that well understood. There are many clinical studies ongoing so well know soon

Overall this is a really promising development because solid tumors are just really tough. There will be a lot more to see in this field the next few years

And men. Although cancer is usually referred to by its location, this is actually much less relevant to its treatment than the type of cancer it is. Although men only get breast cancer rarely, this treatment method will be applicable to many other cancers.

Good news for everyone really. Men can also get breast cancer, and immunotherapy treatment is applicable to many other cancer types.

With those in the U.S. subsidizing the rest of the world.

It's already known what the expected pricing for CAR-T therapy will be, considering the first of these therapies was approved last year for pediatric leukemia (KYMRIAH/tisagenlecleucel). Expect around $475,000.