

Cancer vaccine begins Phase I clinical trials - interconnector
https://www.seas.harvard.edu/news/2013/09/cancer-vaccine-begins-phase-i-clinical-trials

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epistasis
Unlike most vaccines, including the HPV vaccine meant to prevent cervical
cancer, this is not prophylactic, it's not meant to prevent cancer. Rather,
it's a therapy to get rid of cancer once you have it by targeting your immune
system towards cancer cells.

Many (most?) cancers have some degree of immune system involvement. In early
stages of cancer, the immune system often attacks tumor cells. In later stages
of cancer, tumor cells can evolve the behavior of secreting signals to attract
the type of immune cells that can support the tumor by doing things such as
promoting blood vessel growth. We know a _lot_ about the immune system, and I
would venture that we understand more of the immune system's complexity than
any other system in the body, but we still don't know all the dynamics. For
example, we know the development pathways from blood stem cell to
differentiated immune cells, but not all the key factors, or how to push it
just this way or that.

This is not the first cancer vaccine, but it is an interesting new way to
attempt to reprogram the immune system.

~~~
dakrisht
"I would venture that we understand more of the immune system's complexity
than any other system in the body"

NO - this is a completely and profoundly FALSE statement.

We have learned quite a bit about the immune system in the past decade or so
but it is still one of the most mysterious systems in the entire body. The
immune system is a black box from the standpoint of most clinicians today.
It's an _incredibly_ overwhelming and complex system with dozens of
interacting cell types and different molecules spewing into our bloodstream;
with each of those cells containing tens of thousands of genes whose activity
is dependent upon dozens of factors.

So it is far from being understood. But the research and technology is
promising. Immunologists today still perform the same tests they did in the
1960s outside of advanced and experimental immune studies done at the
university level.

Your generic explanation of cancers is also incredibly incorrect.

~~~
epistasis
You seem to be mistaken, and responding to something I did not write. I did
not say that we understand its complexity, I said that we understand more of
it's complexity than any other body system. The depth and complexity of
immunology as a field is evidence of that. My point was that despite having
advanced our knowledge here more than in other parts of molecular biology, we
still can't control it. What do see as incorrect in those statements?

Also if you don't know about immune involvement in cancers, I'd recommend
catching up with the past decade. I pointed out two of the ten Hanahan &
Weinberg hallmarks of cancer, so this isn't exactly old news.

[http://download.bioon.com.cn/upload/201105/22131853_2957.pdf](http://download.bioon.com.cn/upload/201105/22131853_2957.pdf)

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haldujai
Funny that this comes out the day after GlaxoSmithKline's melanoma vaccine
failed in phase III.[0]

Some science background on how these work. The idea is that some cancer types
express specific proteins that can theoretically be targeted by your immune
system, similar to how your immune system can target proteins from the
Influenza virus. The goal of these vaccines is to make your immune system
recognize this protein (called an antigen) and mount an immune response to
kill all the cancer cells expressing the antigen (usually unique to tumour
cells).

The problem is in inducing the immune response, usually these antigens don't
mount strong immune responses so the attack is too slow relative to the rate
that cancer cells divide and spread. Sometimes you also end up stimulating the
wrong immune response, as the human immune response is quite complicated. In
fact, tumors naturally stimulate inflammation and angiogenesis (immune
responses) to spread! To make matters worse, some tumours even suppress the
capability of immune cells to fight in the local area, rendering this vaccine
useless.

The normal operating procedure for these vaccines is to remove some immune
cells from the patient, cause them to become sensitive to a specific antigen,
mix them with an immune system stimulant and inject them back into the
patient. The ultimate goal of all of these methods is to improve the
immunogenicity (ability of the vaccine to elicit an immune response) of
vaccines, these guys are not making a new vaccine. Rather, this is just a new
delivery method.

A very promising drug called Stimuvax by Merck which used liposomes (and had
100% regression in mice vs 50% in this study) to increase immunogenicity
failed as well[1] so this should be taken with great caution, researches were
overly optimistic on previous vaccines such as Stimuvax. Although the idea for
the Harvard/Dana-Farber study is incredibly novel.

[0][http://www.gsk.com/media/press-releases/2013/the-
investigati...](http://www.gsk.com/media/press-releases/2013/the-
investigational-mage-a3-antigen-specific-cancer-immunotherap.html)
[1][https://en.wikipedia.org/wiki/Stimuvax](https://en.wikipedia.org/wiki/Stimuvax)

~~~
dnautics
one dangerous thing is that most conventional cancer drugs cause
immunosuppression (usually bone marrow suppression) so if you're taking these
cancer vaccines you're going to be forgoing conventional treatments for the
duration that you're on the vaccine. But if they have a higher success rate it
would obviously be worth it; even if it has the same success rate since the
vaccines would likely have less side effects.

~~~
haldujai
This does not appear to be correct, while one might logically conclude that a
drug causing suppression would negate the effects of adoptive immunotherapy
this doesn't appear to be the case.

Recent research (see below) suggests that apoptosis from chemotherapy may
actually strengthen the immune response. The same group also conducted pre-
clinical trials and observed that immunotherapy directly after chemotherapy
was significantly more effective than either group alone or immunotherapy
before chemotherapy.

If you do a literature search for adoptive immunotherapy in immunosuppressed
patients you will find more studies. The only contraindication appears to be
in patients with completely eliminated immune systems, which rarely happens
because of chemo.

[http://www.discoverymedicine.com/Robbert-G-Van-der-
most/2009...](http://www.discoverymedicine.com/Robbert-G-Van-der-
most/2009/07/25/combining-immunotherapy-with-chemotherapy-to-treat-cancer/)

Edited to clarify / change tone.

~~~
dnautics
cites two most relevant papers, one of which is specifically about the
strategy to replace the chemotherapeutically depleted T cells with in vitro
expanded ones, post chemotherapy. It's certainly possible, though, not enough
studies have been conducted, and will probably depend on which
chemotherapeutic compound is administering (small molecules tend to have
differential spectra of activities). Doxycycline, in mice in at least one
study was shown to have no particular effect on immunotherapeutic effect.
Gemcitabine, which does do some immunosuppression but doesn't activate BER -
so it only affects a subset of immune cells, does potentiate immunotherapies.

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baldfat
This is only for one form of skin cancer.

I think the word cancer really is used to broadly and most people believe that
cancer = cancer when in fact cancers vary widely. Sarcoma cancer is so
different than say Leukemia that one trial that help one has zero impact on
the other.

In cancer it is the scientific name that is so important to understand what is
happening. I ask people what kind of cancer they have and they say I don't
know its cancer my doctor knows and I just cry on the inside.

~~~
pndmnm
Exactly correct. A great quote I heard once is "asking a scientist when
they'll find a cure for cancer is like asking a mathematician when they'll
find a solution for equations."

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tokenadult
"The goal of the Phase I study, which is expected to conclude in 2015, is to
assess the safety of the vaccine in humans."

This is a fairly written press release, which besides the hopeful language
common to any university press release about science research[1] manages to
mention how preliminary this research still is. Many treatments that show
promise in animal models do not ultimately have clinical usefulness for human
patients. It would be wonderful if this approach to treating cancer is shown
to be safe for human beings, which is the issue explored in a phase I clinical
trial. Then further research will have to explore whether or not this approach
is effective in human patients--which is not a sure thing even if it is
effective in mice. After that, doctors will have to evaluate the treatment's
overall safety and effectiveness compared to all other treatments available by
the unknown future date when some new treatment reaches clinical use. There
will also be the issue, of course, that two kinds of treatment may have
similar safety and effectiveness profiles but differ radically in cost.

All in all, good news at the first step, with a lot more to be found out
before we know whether this will help us dodge the bullet of cancer in our own
lifetimes.

[1]
[http://www.phdcomics.com/comics.php?f=1174](http://www.phdcomics.com/comics.php?f=1174)

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rquantz
It looks like the more interesting part of this article is the accelerated
process to move from early research to human trials. We have lots of ways of
curing cancer in mice that never panned out in humans, but we have a better
chance of finding solutions that work if we can remove some of the impediments
to moving forward with trials. Faster progress is dependent on decreasing the
time each iteration takes.

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jdmitch
_50 percent of mice treated with two doses of the vaccine...showed complete
tumor regression._

I would have thought clinical trials would require a higher success rate... is
it only because it's the last resort and patients would otherwise die anyways?

~~~
user24
I imagine that the success rate varies according to the disease. If it was a
flu vaccine then it would be laughed out at 50%, but for cancer I'm guessing
50% is a mindblowingly awesome success rate.

~~~
sswezey
My mother just died of ocular melanoma, but was in a trial for all melanomas.
The trial drug had an effective rate of 40% and that was considered a huge
increase over the previous of about 15-20%. 50% for a melanoma _vaccine_ is
great.

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ThomPete
*

1 point by ThomPete 0 minutes ago | link | edit | delete

As someone with more than a thousand moles and already one melanoma i am
interested in knowing how to participate in such a thing. reply

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na85
Keep in mind that Phase 1 clinical trials are very very easy to pass.

~~~
sandipc
Phase I trials are also primarily concerned with safety, not efficacy

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Macsenour
I'm interested in the other 50%. No affect? Less affect?

~~~
consider_this
I'd like to know this too.

If the assumption is that they are marching to death prior to vaccine
administration can it get much worse than that?

~~~
hrkristian
Considering melanoma is lethal, and the treatment (radiating away the entire
immune system) bring very risky, this new treatment has the potential to both
lower the risk and increase survival rates. I'll be very interested to see if
the side-effects are of any concern, or if we're one step closer to a cure.

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thelettere
There already is a cancer vaccine. It's called "Don't eat industrialized
crap".

Cancer is virtually non-existent in tradition non-industrial tribes and
societies. And yes many in those culture do grow just about as old as we do.

~~~
Volpe
I think you are going to need to provide some citations.

Which tribes/societies? What is their cancer rate? What are they not consuming
that we are? (who are we?)

Wasn't steve jobs a complete freak with food consumption? (i.e. he didn't eat
industrialised crap)...

~~~
thelettere
Two good referenced articles:

[http://wholehealthsource.blogspot.com/2008/07/cancer-
among-i...](http://wholehealthsource.blogspot.com/2008/07/cancer-among-
inuit.html)

[http://wholehealthsource.blogspot.com/2008/07/cancer-in-
othe...](http://wholehealthsource.blogspot.com/2008/07/cancer-in-other-non-
industrialized.html)

As far as what they're consuming - sugar, processed oils and processed grains
are the most widespread aspects of the industrialized diet, and therefore the
best suspects. Try finding a processed "food" product without either sugar or
an industrialized oil.

Jobs only started experimenting with weird diets after he became an adult.
Also, while industrialized crap is likely the primary culprit, other things
contribute - sedentary lifestyle and lacking basic necessary nutrients (Jobs
experimental diets are like nothing I've ever heard of any non-industrial
tribe or society eat).

~~~
Volpe
That's a blog, from 2008, with no citations itself, and no claim of original
research. So essentially it's opinion. It is confusing correlation with
causation. Westernisation brought "cancer diagnosis" with it. So of course
cancer rates increased, because before they "just died", then they "died of
cancer". The rate of cancer didn't change, the rate of diagnosed cancer did.

Your body needs sugar (through various sources like carbs, or protein)... so
sure if you cutout sugar, you won't get cancer (because you will die of
malnutrition).

I'm not sure what "industrialised oil" is... how does it differ from regular
oil? What about it in particular that makes it carcinogenic?

Jobs also didn't have cancer until he was an adult... are you suggesting he
had some how set his body up into a condition ripe for cancer to develop? That
implies that if you've ever tried "industrialized food" (in your entire life)
it's already over for you, so don't worry about it.

What about children born with cancer? Is that because of their mothers diet
(or their mothers diet when their mother was a child herself)? Simply by
following your reasoning I've just ruled out a HUGE proportion of the
population who don't have to worry, because the damage is already done.

Do you have any academic sources on the subject?

~~~
thelettere
There are several citations in those posts, and a bazillion in the book I
posted below.

Your attitude is all wrong though, and that is what needs fixing, above and
beyond your knowledge. You ask straw man questions - you know I'm talking
about added sugar. As for oil, why don't you look at the label of any
processed food and then do some research on how these oils are produced? You'd
discover how much worse americans health has gotten as these processed oils
have largely replaced butter and animal fat as sources of lipids.

Also you do not appear familiar with how nutritional studies work and the
difficulties of establishing causation. You cannot simply lock someone in a
room and force them to only eat certain foods, and it is really really
expensive to do longitudinal studies. We really know next to nothing based on
controlled experiments on chronic conditions simply because of their
limitations - but you combine the correlationary studies with evolutionary
theory (especially natural selection) and studies in medical anthropology (as
cited in those links) and you have as clear-cut a case as you can get in
nutrition.

Groups that don't eat processed crap get cancer and the metabolic syndrome in
ridiculously high numbers. Groups that don't eat processed crap don't get
these diseases.

Groups that don't eat processed crap, but then suddenly are introduced to
sugar and flour find their chronic health conditions going to the shithole.
There is not example that I know of the contrary.

That's all the proof I need.

------
bneato
I Am Legend?

~~~
dnautics
that was a cancer-curing _virus_ /gene therapy, not a nonreplicating molecule
that stimulates your own immune system.

