Cancer vaccine begins Phase I clinical trials | Hacker News Reader

Cancer vaccine begins Phase I clinical trials

seas.harvard.edu

169 pointsinterconnector40 comments

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.

"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.

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

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

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.

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.

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.

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.

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."

"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

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.

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?

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.

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.

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.

> 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?

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.

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

Presuming that each treatment has an independent chance of success.

Actually it's more than likely that the combination will reduce the chance of success as chemotherapy will wipe out the immune system (generally). Although some groups have shown very preliminary results that the combination may work it has to be given in a specific timeframe (in the order of days) and would work in specific subsets of the population.

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

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

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.

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

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

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

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

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?

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.

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.

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)

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.

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)...

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).

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?

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.