
The Next Wave of Immuno-Oncology - pseudolus
https://blogs.scientificamerican.com/observations/the-next-wave-of-immuno-oncology/
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suddenseizure
I've been following this field with great interest since my wife was diagnosed
with brain cancer.

It seems many types of cancer can evolve resistance to treatment with a single
type of immunotherapy. Similar to how HIV quickly evolved resistance to
treatment by one ARV (antiretroviral).

But HIV can be kept in check by a cocktail of 3 ARVs simultaneously. And
there's some recent research from Mass General where they managed to eradicate
brain tumors in mice using 3 different immunotherapies simultaneously:
[https://advances.massgeneral.org/neuro/journal.aspx?id=1263](https://advances.massgeneral.org/neuro/journal.aspx?id=1263)

> Dr. Curry's group describes "a likely oversimplified, but reasonable"
> summary of the mechanism of the triple therapy: GVAX expands the number and
> diversity of activated tumor-specific T cells and increases the number of
> intratumor CD8+ T cells, while PD-1 inhibition further invigorates the
> effects of those mobilized cells. Meanwhile, agonist anti-OX40 continues to
> skew systemic and tumor microenvironments toward Th1 immunity, suppress
> regulatory T cells and prevent T cell exhaustion.

Hopefully this is a way forward for treating humans too!

~~~
war1025
Looking through your post history, it seems you wife is doing much better than
my dad did with his brain cancer. I assume then that it isn't glioblastoma.
That shit is nasty.

Anyway, I hope things continue to remain reasonably in check for her. Cancer
is a terrible thing.

~~~
suddenseizure
Yes, we are relatively lucky that it's a low grade glioma. Sorry to hear about
your dad, GBM is a monster.

The oncologist told us life expectancy is around 15 years which, while ~10x
better than GBM, is a pretty disappointing thing to hear when you're in your
early thirties. But that number comes from looking back at people diagnosed in
recent decades, so we're really hoping that new treatments will change the
equation going forward.

~~~
BioMeditate
Do you follow the standard of treatment given by the doctor? What about diet
modifications (ketosis) or other supplements (metformin, etc)?

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aaavl2821
I don't know this company very well but quickly looked at their website after
reading that the company authored this article. They recently issued a press
release with the headline that 4 of 5 patients treated with their drug had a
partial response.

Reading further in the press release shows that 10 total patients were
treated, 8 have been assessed, and one of those partial responses was
unconfirmed. I haven't looked at the data and don't know the indication well
enough to know it 3 or 4 partial responses from 10 patients is good. However i
find the company's positioning of the data a bit misleading. For what it's
worth, the stock is down a good amount since they announced this data

The wording of that study update combined with the excited yet data-light SA
article is a bit concerning. I hope this does not make patients think this
potential therapy is more promising than it actually is

[http://ir.adaptimmune.com/phoenix.zhtml?c=253991&p=irol-
news...](http://ir.adaptimmune.com/phoenix.zhtml?c=253991&p=irol-
newsArticle&ID=2397170)

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apathy
JFC it’s a literal adaptimmune ad. “At Megaconglomco Inc, we use our patented
pan-galactic gargleblaster fragments...”

Here I thought we were going to see something like Steve Forman’s work on
CAR-T in glioblastoma, or allo-NK, or diet-based “priming” and the like, but
noooooo...

Not cool at all, SA

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drdrey
With a grain of salt:

> ABOUT THE AUTHOR(S)

> Rafael Amado

> Rafael Amado is president of research and development at Adaptimmune.

~~~
maxharris
Why the grain of salt? Doesn't the fact that they're actually working on the
problem make them _more_ credible, rather than less?

Yes, there's money involved, to be sure. However, on your view, does the fact
that I get paid to write software disqualify me from speaking about software
with credibility?

~~~
jessriedel
It's not about disqualifying anyone or necessarily about money. It's just a
matter of noting bias, whether from money or acclaim.

For instance, if an academic works in a particular area of chemistry, they are
more predisposed to say their area will have big important contributions to
society in the future than a random chemist would.

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astazangasta
I am skeptical that CAR-T therapy will go anywhere with solid tumors. Blood
cancers and solid tumors are extremely different - they are basically
different diseases. First, blood cancers have very few mutations (< 10); solid
tumors may have tens of thousands. This means that blood cancers are a lot
less heterogeneous than solid tumors. CAR-T cells are basically like a very
specific kind of gun - you can say, "kill anything with protein X". But we've
tried targeted therapies in solid tumors; they don't work, because the tumors
usually have enough genetic heterogeneity that they can just evolve around the
therapy. This is likely to be the case with CAR-T therapy as well.

Solid tumors also have the advantage of not being in the blood (obviously) -
this makes them much harder to target with anything, especially circulating
cells, which would have to extravasate and infiltrate the tumor itself. Blood
is very accessible - you can just inject stuff into it. Heck, we have machines
that can take blood out of the body, spin out whatever fractions we want, and
put it back in all in one go.

Finally, blood cancers also have no microenvironment; they are circulating in
the blood. A solid tumor can recruit and reprogram all sorts of quisling cells
to cloak itself. These cells do all kinds of immunosuppressive things that we
don't understand.

The main problem with the solid tumor is its complexity and its adaptive
potential. CAR-T cells are a magic bullet - but the magic bullet can only kill
one thing, not the many-headed thing that is a tumor. To beat the solid tumor
I believe we need to fight it with something that has the adaptive potential
of the tumor itself - i.e., the adaptive immune system.

For this reason I think we're more likely to see success by recruiting the
native immune system. So far we've done this via checkpoint blockade. This
also has its limits - unhooking immune checkpoints is like unchaining a mad
rottweiler. It might kill the tumor, but it might just as well kill you.

Where I'd like immuno-oncology to go is understanding the mechanisms of immune
evasion (i.e., what the tumor is doing to suppress the immune system, which
should be mopping up cancerous cells, but isn't) and suppressing those. That
way we can recruit the immune system to do its job without also causing it to
damage the rest of the body.

But we don't even have an understanding of the immune makeup of the tumor yet,
let alone how the tumor is recruiting and reprogramming immune cells to
suppress the immune response. If we get there I think we'll see some real
progress, but it will take a lot of work. It remains to be seen if we have the
patience to do that work before we give up and move on to the next drug fad.

