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Saturday, June 2, 2012

Macklin Medical Mission - The PD-! Story Continues

Macklin Medical Mission [New drug helps body’s Defence system Fight Cancer] New England Journal of Medicine Following on the very important path-finder work of Dr. Carl June at the University of Pennsylvania Oncology Clinic at the Abramson Oncology Research facility in Philadelphia and their published finding in the The New England Journal of Medicine on “translational white blood cellular therapy” in May of 2011 we now have the similar work being done by Dr. Suzan Topalian of the John Hopkins University in Baltimore Maryland - 1. One of the great frustrations for researchers in the war on cancer is that the body’s own defence system does not do a better job fighting the disease. Tumours, it turns out, have a molecular shield that repels attacks from the immune system. Now, a new study says, an experimental drug is showing promise in disabling that shield, unleashing the immune system and causing shrinkage of some lung, skin and kidney cancers that had defied treatment with existing drugs. “We are seeing responses in heavily treated patients — three different cancers, one drug,” Dr. Suzanne Topalian, a melanoma specialist at Johns Hopkins University and lead investigator in the study, said in an interview. “This is a group of patients whose life expectancy was measured in a few months.” The results are from an early clinical trial, and it is not clear whether the drug, developed by Bristol-Myers Squibb, will actually help people live longer. But Topalian said she was optimistic because when tumours did shrink, they often did not grow back again for more than a year. The study was discussed Friday at a news conference at the annual meeting of the American Society of Clinical Oncology and is being published online by the New England Journal of Medicine. The drug, which now goes by the unwieldy code name of BMS-936558, blocks a protein called PD-1. Such PD-1 inhibitors “could be the most exciting clinical and commercial opportunity in oncology,” analysts at Leerink Swann wrote last month. That is partly because such drugs might be able to treat a variety of cancers [including tumours found in breast cancers]. Bristol-Myers said it intended to begin more clinical trials later this year and early next year aimed at winning approval of the drug to treat non-small-cell lung cancer, kidney cancer and melanoma, which is a deadly skin cancer. Others pursuing drugs that block the action of PD-1 include Merck; the Genentech unit of Roche; Glaxo Smith Kline, working with a small Maryland company called Amplimmune; and Teva working with an Israeli biotech company, CureTech. The early trial, paid for in part by Bristol-Myers, involved 296 patients with various advanced cancers. Tumours shrank significantly in 18 percent of the lung cancer patients, 28 percent of the melanoma patients and 27 percent of those with kidney cancer. Those rates compare favourably with some existing drugs, according to Leerink Swann. But the drug did not appear to work for a small number of patients with prostate or colon cancer. And larger studies will be needed to determine whether freeing the immune system leads to side effects, like attacks on parts of the body besides the tumour. In terms of side effects, about 14 percent of the patients experienced a severe side effect and three patients died from inflammation of the lung that was apparently tied to the drug. Still, the results are an improvement to the approach of harnessing the immune system to fight cancer, a field that has had a history of failures. The process works like this - PD-1, which stands for programmed death 1, is a protein on the surface of activated T cells, the warriors of the immune system [carried by white blood cells]. If another molecule, called PD-L1, binds to PD-1, the T cell dies or becomes docile. This is apparently a way that the body regulates the immune system, to avoid an overreaction. But many cancer cells make PD-L1, which allows them to disarm the T cells just as they have been “informed by the body of an invading cell” and are coming to attack the tumour. The Bristol drug is a monoclonal antibody that blocks PD-1 from binding to PD-L1. Bristol-Myers won approval last year for a drug that removes a different brake on the immune system. That drug, Yervoy, can prolong the lives of people with melanoma [skin cancer], but the unleashed immune system can also lead to severe side effects, like colitis PD-1 blockers appear to free up the immune system only around the tumour, rather than more generally. That could mean that the PD-1 will have “fewer side effects and greater anti-tumour activity,” than drugs like Yervoy, Dr. Antoni Ribas, a melanoma specialist at the University of California, Los Angeles, said in an editorial being published in the New England Journal of Medicine. An Important Note: There is preliminary evidence that PD-1 blockers will not work in people whose tumours do not make PD-L1, as determined by studying a biopsy sample. That might allow the drug to be used only for patients most likely to benefit, researchers said. - - - - - - 2. A type of drug that helps the body's immune system attack tumours 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 tumours 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 tumour'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 tumour and signalling the immune system to attack. Researchers have hypothesized that giving people with tumours 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, multi-center 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, tumours 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 multi-center 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 tumour samples from 42 of the patients receiving anti-PD-1, nine of 25 who responded had PD-L1 on their tumours, 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 immuno-therapy drugs. One way to do that may be to combine them with other treatments, Topalian says. - - - - - - - - - Clearly, what is needed in Canada is a comprehensive and integrated cancer control strategy outside of the control of the “cancer industry” to set and pursue a strategic methodology of promotion, prevention and screening of specific targets to not only get us back on track – while at the same time reviewing new cancer treatments – not just the reworking again and again two very olde sytems as we currently are – buty especially that of stem cell research and working with the body’s own defensive system – the white blood cel;s modified with “adepts” – re-introducing them back into the body in a new highly successful treatment to bring about the necrosis of cancer cells and tumours now under going very successful clincial trials which started in March of 2011 and being monitored by the Macklin Medical Mission in Canada. Your choice now is very simple – both you the private citizen, and the private corporation can decide on who and what to fund. We at the Macklin Medical Mission choose to raise funds for the support of bio-research dealing with T-Cells combined with white blood cells for the translational therapies now available and being developed to fight cancer rather than the harash and caustic methods used in archaic treatments found in radiology and chemotherapy with all their side effects especially for children and the elderly.The ethics are also simple – choose “inept” or “adept”. Thank you. Please note that this is a private sector initiative. Like so many research initiatives, the Government will catch up only when it decides to do so. They are always late to the table and cancer patients are dying daily because of it. Thank you for your financial support. Eric J. Macklin B.Com., FICB, FCSI, FMA, UE The Macklin Medical Mission [Est 1886] Chairman The Nancy-Griffon Foundation Inc [Est 1975] Canada YouTube: Macklin Medical Mission – Cancer Cure