Cancer vaccine begins Phase I clinical trials

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

by interconnector • 13 years ago

169 40 13 years ago

seas.harvard.edu

jdmitch• 13 years ago

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• 13 years ago

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• 13 years ago

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.

dnautics4• 13 years ago

unfortunately, 50% in mice is rather low for cancer even. You usually want to start out at 70-80% in mice for cancer. If you get 50% in humans that's a great success rate, but not in mice. The reason for this is that the mouse model is called a xenograft model, you take a human cancer and implant it into the mouse. Typically, you are running the experiment on mice implanted with the cell line that gave the best hit in your in vitro model, so it better do darned well, relatively speaking.

I could be wrong about this though, usually the xenograft is done in immunocompromised mice (because otherwise the mice would reject the human cancer line)... So there could be complicating factors.

dragonwriter• 13 years ago

I would have thought clinical trials would require a higher success rate...

Why?

If its better than than the alternatives (including consideration of side effects), why would it need to be completely successful in more than 50% of cases to pass a trial?

jawns• 13 years ago

It depends on the percentage of people who show complete tumor regression with existing approaches, and on the relative costs and side effects. For instance, if only 25 percent of people show complete tumor regression with existing approaches, then getting the number up to 50 percent is a huge deal. Or, if the percentage is in line with existing approaches but the cost is much lower, that's another big win.

im3w1l• 13 years ago

Maybe you could even get 1-(1-0.25)*(1-0.5)=0.625 complete tumour regression with a combined treatment.

zdean• 13 years ago

This issue was well-presented and discussed a few days ago:

https://news.ycombinator.com/item?id=6375169

Alex3917• 13 years ago

Clinical trials only require you to prove your treatment is better than a placebo, you don't need to prove that it's better than existing drugs.

epistasis2• 13 years ago

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• 13 years ago

"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.

epistasis2• 13 years ago

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

Macsenour• 13 years ago

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

consider_this• 13 years ago

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• 13 years ago

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.

kamjam• 13 years ago

I guess it depends on the exact side effects, but if it causes more pain and suffering, then a more painful death is worse than a peaceful one, and on a per person basis - some may take the view they will die anyway and it's worth the risk as a last resort. But good question from the OP.

cowsandmilk• 13 years ago

looks like they died after 55-60 days, instead of dying after <30 days.

Source Fig 7B : http://stm.sciencemag.org/content/1/8/8ra19/F7.large.jpg

For those without access to science: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872791/figure/F...

(Note the figure quality on pubmed central is really crappy for some reason, but you should get the point, survival from 2 vaccinations is 47% (7/15 mice) shown by the blue line, black dotted line is blank injections)

tokenadult• 13 years ago

"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

rquantz• 13 years ago

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.

bneato• 13 years ago

I Am Legend?

Lifescape• 13 years ago

That's my cue to go get a puppy.

booruguru• 13 years ago

I have a sense of humour, so I gave you an upvote.

dnautics4• 13 years ago

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

haldujai3• 13 years ago

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... [1]https://en.wikipedia.org/wiki/Stimuvax

dnautics4• 13 years ago

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.

haldujai3• 13 years ago

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...

Edited to clarify / change tone.

ThomPete• 13 years ago

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

baldfat• 13 years ago

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• 13 years ago

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."

na85• 13 years ago

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

sandipc• 13 years ago

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

thelettere4• 13 years ago

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.

Volpe2• 13 years ago

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)...

thelettere4• 13 years ago

Two good referenced articles:

http://wholehealthsource.blogspot.com/2008/07/cancer-among-i...

http://wholehealthsource.blogspot.com/2008/07/cancer-in-othe...

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).

thelettere4• 13 years ago

Cancer vaccine begins Phase I clinical trials

Related Stories