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Cancer 'vaccine' eliminates tumors in mice, researchers find
medicalxpress.com ^ | 01/31/2018 | Stanford University Medical Center

Posted on 01/31/2018 2:05:50 PM PST by Red Badger

Scientists devised a pinpointed immunotherapy regimen that eradicated tumors throughout the body in mice. Credit: Sagiv-Barfi et al., Science Translational Medicine (2018)

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TOPICS: Business/Economy; Health/Medicine; Pets/Animals; Science
KEYWORDS: cancer; cancercure; cancertreatment; cancervaccine; immune; immunesystem; immunotherapy; lymphoma; mice; tumor
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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 currently 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.

Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which will be 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 anticancer 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.

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.

Explore further: Researchers discover new approach to stimulate an immune response against tumor cells

More information: I. Sagiv-Barfi el al., "Eradication of spontaneous malignancy by local immunotherapy," Science Translational Medicine (2018). stm.sciencemag.org/lookup/doi/ … scitranslmed.aan4488

Journal reference: Science Translational Medicine

Provided by: Stanford University Medical Center

1 posted on 01/31/2018 2:05:51 PM PST by Red Badger
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To: Red Badger

Cancer has been cured in mice many many times.

The key here is the model, the tumor model. I haven’t read the article yet, so I can’t comment.


2 posted on 01/31/2018 2:08:09 PM PST by ifinnegan (Democrats kill babies and harvest their organs to sell)
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To: Red Badger

Praying for positive results in humans.


3 posted on 01/31/2018 2:16:04 PM PST by Blood of Tyrants (Conservatives love America for what it is. Liberals hate America for the same reason.)
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To: Red Badger

A squeaker of a treatment, huh.

Humans have a more complicated genome which gives cancer more places to do mischief.


4 posted on 01/31/2018 2:18:50 PM PST by HiTech RedNeck (Tryin' hard to win the No-Bull Prize.)
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To: Red Badger

This must be fairly slow-acting. I recall from having my late, beloved Lab treated for cancer that there is such a thing as too successful with large tumors. That much cell death all at once can have severe systemic effects upon the body, even leading to death of the patient.


5 posted on 01/31/2018 2:26:27 PM PST by RegulatorCountry
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To: Red Badger

Having worked at a Harvard Teaching Hospital for 25 years I can guarantee that in the world of medical research Stanford = serious credibility.


6 posted on 01/31/2018 2:32:34 PM PST by Gay State Conservative (Remember: All Cultures Are Equal!)
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To: Red Badger

Bookmark


7 posted on 01/31/2018 2:33:47 PM PST by airborne (I don't always scream at the TV but when I do it's hockey playoffs season!)
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To: Red Badger

If I run across any mice with cancer I’ll let these guys know...


8 posted on 01/31/2018 2:34:26 PM PST by WayneS (An appeaser is one who feeds a crocodile, hoping it will eat him last. - Winston Churchill)
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To: Gay State Conservative

Yep, they got cred....................


9 posted on 01/31/2018 2:34:41 PM PST by Red Badger (Wanna surprise? Google your own name. Wanna have fun? Google your friends names......)
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To: ifinnegan

A giant leap for rodent-kind.


10 posted on 01/31/2018 2:35:59 PM PST by Moonman62 (Make America Great Again!)
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To: Red Badger

Hopefully the side effects aren’t serious.


11 posted on 01/31/2018 2:36:34 PM PST by <1/1,000,000th%
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To: Red Badger

It’s not a Tumah!


12 posted on 01/31/2018 2:36:40 PM PST by dfwgator
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To: ifinnegan

"A cure for cancer is right around the corner."


13 posted on 01/31/2018 2:37:44 PM PST by Jeff Chandler (TRUMP RULES - KENNEDY DROOLS)
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To: <1/1,000,000th%

Just massive cravings for cheese....................


14 posted on 01/31/2018 2:38:48 PM PST by Red Badger (Wanna surprise? Google your own name. Wanna have fun? Google your friends names......)
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To: RegulatorCountry
there is such a thing as too successful with large tumors

A good friend has lung cancer; a single large tumor in one lung. He's having it treated with daily low-dose targeted radiation and low dose chemotherapy to shrink it. When it gets small enough, they'll hit it with an immune-system based treatment to destroy it completely. Can't use the immune therapy until it gets small.

15 posted on 01/31/2018 2:40:19 PM PST by NorthMountain (... the right of the people to keep and bear arms shall not be infringed)
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To: Gay State Conservative

I like what Trump said last night about very sick people getting access to cutting edge treatments.


16 posted on 01/31/2018 2:41:23 PM PST by Moonman62 (Make America Great Again!)
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To: Red Badger

I wish to alert Moslems that this was developed by dog-
and monkey-descended Jews, so you should avoid using this treatment at all costs.


17 posted on 01/31/2018 2:46:46 PM PST by Ancesthntr ("The right to buy weapons is the right to be free." A. E. van Vogt)
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To: HiTech RedNeck
>> Humans have a more complicated genome which gives cancer more places to do mischief <<

Not altogether clear. While we have more base pairs, they have more genes.

Source:

http://www.biology-pages.info/G/GenomeSizes.html

18 posted on 01/31/2018 2:48:33 PM PST by Hawthorn
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To: Ancesthntr

....and it comes from pigs..............


19 posted on 01/31/2018 2:48:41 PM PST by Red Badger (Wanna surprise? Google your own name. Wanna have fun? Google your friends names......)
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To: Hawthorn

OK, so what is the fundamental measure of the information? The “base pairs” or the “genes” or some statistical evaluation of the content of one or the other?


20 posted on 01/31/2018 2:51:49 PM PST by HiTech RedNeck (Tryin' hard to win the No-Bull Prize.)
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