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Conquering Cancer by Thwarting Tumor's Immune Shield
SccienceNOW ^ | 2 June 2012 | Jocelyn Kaiser

Posted on 06/02/2012 6:06:18 PM PDT by neverdem

Enlarge Image
Vulnerable. A new type of drug blocks a tumor cell's shield (left) against T cells (knights) so that they can attack.
Credit: Ryan Snook,

A type of drug that helps the body's immune system attack tumors is showing promise. In early clinical trials involving several hundred patients with various kinds of advanced cancer, up to one-quarter of those who received the treatment saw their tumors shrink, and some are still alive more than a year later.

The results are the latest good news for so-called immunotherapy treatments that work by overcoming a tumor's ability to evade the immune system. One way cancer cells escape destruction is by producing a protein on their surface, known as programmed death ligand-1 (PD-L1), that locks onto a protein called PD-1 on T cells, a type of immune cell. When the two connect, that prevents T cells from detecting the tumor and signaling the immune system to attack. Researchers have hypothesized that giving people with tumors an antibody (a protein) that blocks either PD-1 or PD-L1 would keep the proteins from engaging and switching off T cells—and a small initial clinical trial of an anti-PD-1 drug confirmed that this strategy holds promise for treating cancer.

So do two larger, multicenter studies of this approach, which are being presented today at the annual meeting of the American Society of Clinical Oncology in Chicago. When a group of 296 patients with five types of advanced cancer received an infusion of an antibody targeting PD-1 every 2 weeks, tumors shrank in 14 of 76 lung cancer patients, 26 of 94 melanoma patients, and 9 of 33 kidney cancer patients—an 18% to 28% response rate. Many patients have responded to the drug for a year or longer. "These are very encouraging signals," says melanoma researcher Suzanne Topalian of Johns Hopkins University in Baltimore, Maryland, a leader of the multicenter study.

In a separate study at Hopkins and elsewhere in which 207 cancer patients received an antibody that blocks PD-L1, 10% to 17% of those with one of three types of cancer have responded, and some patients have responded for at least a year.

As with most early drug studies, the trials were predominantly designed to test safety; more studies are needed to show whether those receiving the antibodies live longer than they would on conventional treatments. (Topalian says the 1-year survival results are encouraging, however. In other studies, advanced melanoma patients on standard treatment lived for 6 to 7 months on average.) And the drugs, both made by Bristol-Myers Squibb, can result in severe side effects: The anti-PD-1 drug caused three deaths from lung inflammation.

Still, the fact that both drugs seem to have a clinical impact "says that this combined [PD-1/PD-L1] pathway is important as a target for cancer therapy," Topalian says. When researchers tested tumor samples from 42 of the patients receiving anti-PD-1, nine of 25 who responded had PD-L1 on their tumors, while none of those lacking PD-L1 on their cancer cells responded. That means a test for PD-L1 could potentially tell doctors which patients should get the drug, much as physicians now routinely test breast cancers to see if they should receive various hormone therapies.

The two trials, whose results are also reported online today in The New England Journal of Medicine, have "broken the ceiling" of a 10% to 15% response rate for a similar strategy that targets a T-cell protein called CTLA-4, says oncologist Antoni Ribas of the University of California, Los Angeles, who wrote an accompanying commentary in the journal. A CTLA-4-blocking antibody called ipilimumab was approved for melanoma treatment by U.S. regulators last year. But it seems to cause more side effects than anti-PD-1 drugs, probably because CTLA-4 is present on T cells in more tissues of the body.

"The biggest feature of all these approaches is that it engages [an immune] memory response, so responses tend to be durable," says Ribas. Still, one significant remaining challenge is to get more patients to respond to the growing number of these immunotherapy drugs. One way to do that may be to combine them with other treatments, Topalian says.

TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: cancer; immunology; pd1; pdli
The second and fourth links are the same.
1 posted on 06/02/2012 6:06:28 PM PDT by neverdem
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To: neverdem

I hope that future trials/research will fine tune the treatment.

2 posted on 06/02/2012 6:32:10 PM PDT by ak267
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To: neverdem

Ipilimumab can work against tumors,
but it is kinda nasty, as it can turn on immune system in
other parts of body, leading to destructive lesions in
those the package insert.

Perhaps of balance of surgery, chemo , radiation, and
immunological augmentation can put a dent in the tumor
expression. Therefore cancer may just become a disease
that can be suppressed on a consistent basis.

3 posted on 06/02/2012 9:19:39 PM PDT by Getready (Wisdom is more valuable than gold and diamonds, and harder to find.)
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To: Getready

Shades of tumor necrosis factor, whose discovery was likened to seeing the light at the end of the tunnel only to discover it was the headlamp of an oncoming train. The body’s attempts to zap the cancer were also ravaging surrounding tissue.

4 posted on 06/02/2012 9:24:58 PM PDT by HiTech RedNeck (Let me ABOs run loose Lou!)
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To: neverdem
Is Big Pharma Ignoring a Potential Cancer Cure? This has stirred some interest.
5 posted on 06/02/2012 9:44:07 PM PDT by WilliamofCarmichael (If modern America's Man on Horseback is out there, Get on the damn horse already!)
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To: WilliamofCarmichael

Thanks for the link.

6 posted on 06/02/2012 10:26:00 PM PDT by neverdem (Xin loi minh oi)
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To: neverdem

I read recently that DMSO can be used to get chemo directly to the cancer cells without damaging good cells. I believe it but the FDA has put a ban on DMSO. I wonder if big pharma will go ahead anyway. If they do I hope it’s very soon because my wife just started year 3 of Stage IV lung cancer.

7 posted on 06/03/2012 7:17:14 AM PDT by New Jersey Realist (America: home of the free because of the brave)
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To: neverdem

bump—killing cancer

8 posted on 06/03/2012 2:30:04 PM PDT by Taffini ( Mr. Pippen and Mr. Waffles do not approve and neither do I)
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