Cancer 'Vaccine' successful on mice

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Cancer 'Vaccine' successful on mice

Post by FaxModem1 » 2018-03-11 03:19pm

Stanford Medicine
Cancer ‘vaccine’ eliminates tumors in mice
Activating T cells in tumors eliminated even distant metastases in mice, Stanford researchers found. Lymphoma patients are being recruited to test the technique in a clinical trial.

JAN 31 2018
Man and woman in lab coats look at a computer screen
Ronald Levy (left) and Idit Sagiv-Barfi led the work on a possible cancer treatment that involves injecting two immune-stimulating agents directly into solid tumors.
Steve Fisch

Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.

The approach works for many different types of cancers, including those that arise spontaneously, the study found.

The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.

“When we use these two agents together, we see the elimination of tumors all over the body,” said Ronald Levy, MD, professor of oncology. “This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”

One agent is already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma. (Information about the trial is available online.)

Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which was published Jan. 31 in Science Translational Medicine. Instructor of medicine Idit Sagiv-Barfi, PhD, is the lead author.

‘Amazing, bodywide effects’
Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anti-cancer treatment in humans.

Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells. Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient’s immune cells to be removed from the body and genetically engineered to attack the tumor cells. Many of these approaches have been successful, but they each have downsides — from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times.

“All of these immunotherapy advances are changing medical practice,” Levy said. “Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumors all over the animal.”

Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.

Levy’s method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.

Cancer-destroying rangers
Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.

The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors.

I don’t think there’s a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system.
Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals’ life span, the researchers found.

Finally, Sagiv-Barfi explored the specificity of the T cells by transplanting two types of tumors into the mice. She transplanted the same lymphoma cancer cells in two locations, and she transplanted a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the growth of the colon cancer cells.

“This is a very targeted approach,” Levy said. “Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T cells are recognizing.”

The current clinical trial is expected to recruit about 15 patients with low-grade lymphoma. If successful, Levy believes the treatment could be useful for many tumor types. He envisions a future in which clinicians inject the two agents into solid tumors in humans prior to surgical removal of the cancer as a way to prevent recurrence due to unidentified metastases or lingering cancer cells, or even to head off the development of future tumors that arise due to genetic mutations like BRCA1 and 2.

“I don’t think there’s a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system,” Levy said.

The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

The study’s other Stanford co-authors are senior research assistant and lab manager Debra Czerwinski; professor of medicine Shoshana Levy, PhD; postdoctoral scholar Israt Alam, PhD; graduate student Aaron Mayer; and professor of radiology Sanjiv Gambhir, MD, PhD.

Levy is a member of the Stanford Cancer Institute and Stanford Bio-X.

Gambhir is the founder and equity holder in CellSight Inc., which develops and translates multimodality strategies to image cell trafficking and transplantation.

The research was supported by the National Institutes of Health (grant CA188005), the Leukemia and Lymphoma Society, the Boaz and Varda Dotan Foundation and the Phil N. Allen Foundation.

Stanford’s Department of Medicine also supported the work.

Okay, for those more knowledgeable, what does this mean? Is this real? Or does it sound too suspicious?
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Re: Cancer 'Vaccine' successful on mice

Post by mr friendly guy » 2018-03-11 08:10pm

Broad principles of using the immune system to target cancers have been around for a while now. Generally though its some drug binding onto parts of a cancer (because its an antibody) and sending out signals to the immune system saying "come attack this thing,", because that's how antibodies work (unlike say, on Star Trek Voyager :D ).

This thing seems to work by telling cells to attack a surrounding area (where they inject the drugs). The cells then recognise the cancer cells as hostile (we don't even know how they recognise the cancer cells, ie which proteins do you deem as "foreign"). If the article is to be believed, now that the immune system realises this is foreign, they can attack cancer around the body as well.

Assuming this works, it would do nicely for solid organ tumours ie breast, prostate, lung etc where there is a solid target to inject into. You might be asking, what are there liquid cancers? :D Sort off. What's counted as a liquid in the body? Well blood. So blood cancers include lymphomas and leukaemias (its a cancer of the blood cells, rather than the liquid component of blood obviously). This could potentially be a bit trickier, however they are going to try it on lymphomas. Lymphomas do provide a solid target, as it does manifest as enlarged lymph nodes, so presumably they will inject into one of those and see.
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Re: Cancer 'Vaccine' successful on mice

Post by fnord » 2018-03-14 11:06am

Really dumb and possibly OT question - what is the difference between the senior author of a paper and the lead author?
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Re: Cancer 'Vaccine' successful on mice

Post by EnterpriseSovereign » 2018-03-14 11:29am

As a concept, cancer Immunotherapy has been around a while. What's unclear is its actual effectiveness as a treatment- what is clear though is that perfecting it is the holy grail of oncology.
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Re: Cancer 'Vaccine' successful on mice

Post by FireNexus » 2018-03-15 12:15am

mr friendly guy wrote:
2018-03-11 08:10pm
Broad principles of using the immune system to target cancers have been around for a while now. Generally though its some drug binding onto parts of a cancer (because its an antibody) and sending out signals to the immune system saying "come attack this thing,", because that's how antibodies work (unlike say, on Star Trek Voyager :D ).

This thing seems to work by telling cells to attack a surrounding area (where they inject the drugs). The cells then recognise the cancer cells as hostile (we don't even know how they recognise the cancer cells, ie which proteins do you deem as "foreign"). If the article is to be believed, now that the immune system realises this is foreign, they can attack cancer around the body as well.

Assuming this works, it would do nicely for solid organ tumours ie breast, prostate, lung etc where there is a solid target to inject into. You might be asking, what are there liquid cancers? :D Sort off. What's counted as a liquid in the body? Well blood. So blood cancers include lymphomas and leukaemias (its a cancer of the blood cells, rather than the liquid component of blood obviously). This could potentially be a bit trickier, however they are going to try it on lymphomas. Lymphomas do provide a solid target, as it does manifest as enlarged lymph nodes, so presumably they will inject into one of those and see.
I feel like from the description it sounds like a potentially nasty bioweapon. Like, it’s described as not cancer-type-specific, so it’s celltype specific. Accidentally get it in a normal muscle, say, and suddenly you’re in a body-wide autoimmune battle with all your muscles. Unless I missed some part where they train it in cultures cells outside the body first to make it effective.
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Re: Cancer 'Vaccine' successful on mice

Post by mr friendly guy » 2018-03-15 10:45am

FireNexus wrote:
2018-03-15 12:15am
I feel like from the description it sounds like a potentially nasty bioweapon. Like, it’s described as not cancer-type-specific, so it’s celltype specific. Accidentally get it in a normal muscle, say, and suddenly you’re in a body-wide autoimmune battle with all your muscles. Unless I missed some part where they train it in cultures cells outside the body first to make it effective.
Bioweapons still need a way to spread effectively though. Consider ricin, which denatures rapidly in air so it can only used if injected. Effective assassination tool, but difficult to weaponise en mass. This treatment for cancer is also injected. We have no idea if it can be spread via a more effective method for reaching mass populations.

But you bring up a good point, its not clear how it trains parts of the immune system to recognise the normal cells in our body as something not to attack. Although an autoimmune disease that it provokes should theoretically be responsive to steroids.
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Re: Cancer 'Vaccine' successful on mice

Post by Broomstick » 2018-03-15 11:30am

mr friendly guy wrote:
2018-03-15 10:45am
FireNexus wrote:
2018-03-15 12:15am
I feel like from the description it sounds like a potentially nasty bioweapon. Like, it’s described as not cancer-type-specific, so it’s celltype specific. Accidentally get it in a normal muscle, say, and suddenly you’re in a body-wide autoimmune battle with all your muscles. Unless I missed some part where they train it in cultures cells outside the body first to make it effective.
But you bring up a good point, its not clear how it trains parts of the immune system to recognise the normal cells in our body as something not to attack. Although an autoimmune disease that it provokes should theoretically be responsive to steroids.
Immune system vs. rest of the body problems is actually the leading cause of serious side effects and even death with the current immune treatments for cancer. And while steroids can help they are not a cure, much less a cure-all. Steroids strong enough to halt these reactions also carry serious side effects and can contribute to morbidity and mortality.

Is trading cancer for an serious autoimmune disease a good trade off? That depends on the person and the disease(s).
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Re: Cancer 'Vaccine' successful on mice

Post by FireNexus » 2018-03-15 12:58pm

mr friendly guy wrote:
2018-03-15 10:45am
FireNexus wrote:
2018-03-15 12:15am
I feel like from the description it sounds like a potentially nasty bioweapon. Like, it’s described as not cancer-type-specific, so it’s celltype specific. Accidentally get it in a normal muscle, say, and suddenly you’re in a body-wide autoimmune battle with all your muscles. Unless I missed some part where they train it in cultures cells outside the body first to make it effective.
Bioweapons still need a way to spread effectively though. Consider ricin, which denatures rapidly in air so it can only used if injected. Effective assassination tool, but difficult to weaponise en mass. This treatment for cancer is also injected. We have no idea if it can be spread via a more effective method for reaching mass populations.
I was thinking of it as an assassination tool. Sudden and extreme autoimmune disease being the way that your target dies, without detectable levels of a causative agent. Seems good if you just want someone dead without making a big ruckus. There are plenty of tools for that, but having a big bag of tricks seems prudent.

It would probably depend on just how sudden and aggressive the immune response is and the tissue affected (a sudden and aggressive immune response to your muscles wouldn’t be great for cardiac health, I imagine, even if you’re treated promptly with steroids that are effective) whether this would be useful in that role if it is as unspecific to cancer as it sounds.
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Re: Cancer 'Vaccine' successful on mice

Post by Broomstick » 2018-03-15 01:59pm

FireNexus wrote:
2018-03-15 12:58pm
It would probably depend on just how sudden and aggressive the immune response is and the tissue affected (a sudden and aggressive immune response to your muscles wouldn’t be great for cardiac health, I imagine, even if you’re treated promptly with steroids that are effective) whether this would be useful in that role if it is as unspecific to cancer as it sounds.
My sister has an auto-immune disease that primarily attacked her heart. No, it's not good for your cardiac health! They've brought it under control, but there are times she bitches about both the limitations the damage has imposed on her, and the side effects of the required drugs, which are about what someone with a heart transplant would have to take. Not that I have a problem with that - everyone has a right to complain once in awhile and I'm willing to listen. If nothing else, it makes my immune issues (severe allergies) seem trivial in comparison.
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Re: Cancer 'Vaccine' successful on mice

Post by fractalsponge1 » 2018-03-15 08:20pm

fnord wrote:
2018-03-14 11:06am
Really dumb and possibly OT question - what is the difference between the senior author of a paper and the lead author?
Generally speaking, lead author is the one with most responsibility for actually doing the work, and senior author is the lead of the lab where most of the work was done and who directs the research overall.

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Re: Cancer 'Vaccine' successful on mice

Post by mr friendly guy » 2018-03-16 07:52am

FireNexus wrote:
2018-03-15 12:58pm


I was thinking of it as an assassination tool. Sudden and extreme autoimmune disease being the way that your target dies, without detectable levels of a causative agent. Seems good if you just want someone dead without making a big ruckus. There are plenty of tools for that, but having a big bag of tricks seems prudent.
Got you now. An assassination tool rather than a WMD. I suppose its possible, although given use of steroids can prolong life in autoimmune disease, the target might last for a while yet. This may or may not defeat the purpose of your assassination attempt ie was it to send a message of don't fuck with us, or to actually get them to die reasonably quickly.
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Re: Cancer 'Vaccine' successful on mice

Post by cadbrowser » 2018-03-20 12:33pm

So...How much will they hike up the price to cure cancer then? Assuming all human trials are more than adequate that is.

How long will insurance companies refuse to pay for this?
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Re: Cancer 'Vaccine' successful on mice

Post by FireNexus » 2018-03-20 05:10pm

cadbrowser wrote:
2018-03-20 12:33pm
So...How much will they hike up the price to cure cancer then? Assuming all human trials are more than adequate that is.

How long will insurance companies refuse to pay for this?
If it’s the only game in town, and works as advertised, they don’t even have to overcharge by the standards of cancer therapy. They will instantly corner the market on almost every form of solid cancer. Something like this working with as many or fewer side effects as first-line treatments today would probably make some biotech shareholders commit suicide from how fast their fortunes crumble.

They’re apparently biologicals (expensive!) but they cure metastatic cancer (big money saver for insurance) and replace equally expensive therapies that often fail to cure.
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Re: Cancer 'Vaccine' successful on mice

Post by Knife » 2018-03-22 11:50pm

Yeah, biologics have made great strides in cancer treatments the last 10-15 years. Mabs and Nibs. Hell, give it another 5 years and we'll all be eating Opdivo and Keytruda on our corn flakes, they are getting more and more indications yearly.

The OP seems like a similar bit.
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Re: Cancer 'Vaccine' successful on mice

Post by Knife » 2018-03-22 11:54pm

cadbrowser wrote:
2018-03-20 12:33pm
So...How much will they hike up the price to cure cancer then? Assuming all human trials are more than adequate that is.

How long will insurance companies refuse to pay for this?
Cancer drugs are... expensive. I routinely give injections that aren't anti neoplastic but support meds that are thousands of dollars a shot. I give infusions that cost more than most new cars. That said, almost every cancer patient doesn't pay anything for them. Medicare, what most cancer patients have for insurance, pays for pretty much any cancer med and support meds in the NCCN guidelines. Pretty much any insurance company will pay for cancer meds. It's bad publicity not to. In the few cases where they don't, most of the companies have programs that give the drugs either pro bono or at a huge reduced price. Again, bad publicity to have someone out there die without meds.

I'm not a huge fan of big pharma, but when it comes to cancer, they do do it right.
They say, "the tree of liberty must be watered with the blood of tyrants and patriots." I suppose it never occurred to them that they are the tyrants, not the patriots. Those weapons are not being used to fight some kind of tyranny; they are bringing them to an event where people are getting together to talk. -Mike Wong

But as far as board culture in general, I do think that young male overaggression is a contributing factor to the general atmosphere of hostility. It's not SOS and the Mess throwing hand grenades all over the forum- Red

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Re: Cancer 'Vaccine' successful on mice

Post by Simon_Jester » 2018-03-26 04:29pm

What are the main factors driving up the cost, in your opinion?

Small synthesis quantities?

Small number of customers at any one time (due to rare cancer types and high fatality rates) meaning that companies have to charge through the nose to recoup their research and testing costs?
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Re: Cancer 'Vaccine' successful on mice

Post by FireNexus » 2018-03-26 11:16pm

I can answer that one a little bit. Biologics are expensive to make, because they have to be more-or-less “brewed” then refined to high purity. This isn’t small molecule poisons like chemotherapy. It’s complex peptides or proteins which have to be created by living biological system, meaning they come with all the assorted detritus of living things and the production runs are more vulnerable than normal chemosynthesis.

Most drugs up until about 15 years ago are “small molecule” drugs that can be made in a chemistry lab with reasonable precision. The newer cancer meds and certain kinds of autoimmune disease treatments are “large molecule” drugs that are more like proteins or complex peptides that mimic proteins. This is also why a lot of the newer plaque psoriasis or arthritis drugs, for instance, need to be injected. Large molecules get shredded by the digestive tract and don’t get absorbed mucosally.
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Re: Cancer 'Vaccine' successful on mice

Post by Esquire » 2018-03-27 10:58am

Also, drug prices can seem crazy if you only look at the production-cost-per-dose because they're retroactively paying for the obscene amounts of money that go into researching these things; a large set of final-phase sister trials (trials of the same drug in slightly different populations or some such) might cost $40,000 each for 10,000 patients in direct costs alone, setting aside the entire administrative backend, any settlement payments that might be required, or the cost of early-phase research, and take more than a decade. This is largely* a result of poorly-designed oversight structures, but the money still has to come from somewhere.

*By which I mean that drug development needn't a priori be so horribly expensive for the same level of safety and scientific integrity, not that our benevolent corporate overlords should be regulated only by the goodness of their own hearts, or something. Just so we're clear.
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Re: Cancer 'Vaccine' successful on mice

Post by Knife » 2018-03-27 11:57pm

Simon_Jester wrote:
2018-03-26 04:29pm
What are the main factors driving up the cost, in your opinion?

Small synthesis quantities?

Small number of customers at any one time (due to rare cancer types and high fatality rates) meaning that companies have to charge through the nose to recoup their research and testing costs?
Fire Nexus pretty much has it. Mono clonal antibodies are expensive due to just what they are and how you make them. That said, price should be coming down soon, the market got hit with a bunch of them and a couple, Keytruda and Opdivo, keep getting new indications for various types of cancers. Herceptin will always just be breast cancer due to what it is, but the market is getting rocked with both new drugs and old drugs that have been studied and cleared by NCCN for treatment on other types of cancers the drug was not necessarily created for.

I joke with the pharma reps that within a year or two we'll be eating Opdivo on our cornflakes.

But also, chemo and biologics are expensive because while cancer is horrible, it's also not a huge slice of the population. It's not like Lisinopril where tens of millions of people will be on it, or coumadin, or scores of other meds. And a lot of the first line meds are cancer specific, or really mutation of a type of cancer specific.

So yes, overall low population of cancer, multiple types, different meds for each, and variable survival rates. Though I'll add we're getting pretty good at most types. Pancreatic being one of the big ones we aren't good at.
They say, "the tree of liberty must be watered with the blood of tyrants and patriots." I suppose it never occurred to them that they are the tyrants, not the patriots. Those weapons are not being used to fight some kind of tyranny; they are bringing them to an event where people are getting together to talk. -Mike Wong

But as far as board culture in general, I do think that young male overaggression is a contributing factor to the general atmosphere of hostility. It's not SOS and the Mess throwing hand grenades all over the forum- Red

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