The newest cancer therapies don’t work on everyone. Now, doctors have a clue why

first_img About the Author Reprints The reason that doesn’t happen in some 80 percent of cancer patients is that their tumors don’t have enough neoantigens to attract T cells. The total number of neoantigens roughly predicts whether cancer patients respond to immune-blockade drugs like Keytruda and Opdivo, a similar agent from Bristol-Myers Squibb, but the connection isn’t perfect.“You see cases with a lot of neoantigens who don’t respond, and some with few neoantigens who do respond,” said Dr. Eliezer Van Allen, a clinician-scientist at the Dana-Farber Cancer Institute in Boston and an author of the new study, which was published in Science.The number of neoantigens is only part of the story. This study goes beyond previous ones in showing that when neoantigens are found throughout a tumor rather than in some cells only, patients have the best shot at benefitting from immunotherapy. And that’s true even if there are relatively few neoantigens.For instance, 12 out of 13 study participants whose lung cancers responded to Keytruda not only had a lot of neoantigens (more than 70), most of those neoantigens were present throughout the tumor. They attracted tumor-attacking T cells, which Keytruda let in, destroying enough of the cancer to send the patients into remission.In contrast, 16 of 18 lung cancer patients who did not benefit from Keytruda either did not have many neoantigens or had neoantigens that were present in only some tumor cells. Even a patient with a huge number of neoantigens relapsed after only two months; more than 80 percent of his mutations were found in only some tumor cells.“The tumors that we think will respond the best [to Keytruda and similar drugs] have a certain neoantigen burden, but those neoantigens have to be in almost every tumor cell,” said Dr. Charles Swanton, a cancer geneticist at the Francis Crick Institute in London, who, with immunologist Sergio Quezada of University College London, led the study. Swanton, Quezada, and three other coauthors also filed several patents that cover methods for identifying neoantigens and predicting the prognosis of cancer patients accordingly. Sharon Begley The scientists got similar results in melanoma: The fewer total neoantigens, and the more scattered around a tumor they were, the less patients responded to Yervoy, an immunotherapy drug from Bristol-Myers Squibb.Notably, melanoma patients who had already received chemotherapy drugs or radiation had large numbers of neoantigens, apparently induced by those treatments, but each one was found in only a few tumor cells. Standard cancer therapies “may be causing changes in tumors that might not be helpful” in terms of making patients respond to subsequent immunotherapy, Swanton said.The evidence is too preliminary for doctors to act upon, but the findings suggest that some patients might be better off skipping slash-and-burn chemo and going right to immune-modulating agents. Plus, physicians may be able to tell, by analyzing neoantigens in cells taken via standard biopsy, whether a patient has a good chance of being helped by those drugs.The study results can also “be used to inform the development of personalized cancer vaccines,” said Van Allen. These experimental treatments, which are tailor-made to a patient’s neoantigen profile, are being tested in clinical trials now. They are designed to stimulate the immune system to attack neoantigens on tumors, but scientists hadn’t been sure which neoantigens would make the best vaccines.“This is a very important paper,” said Dr. Elizabeth Jaffee, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who was not involved in the study. “It addresses a critical question in this field: Are all [neoantigens] equally important to the immune system or is there a way to sort this out?”The suggestion that the best neoantigens are found throughout the tumor “makes the case that we need to sample more of the tumor before predicting which expressed mutations are most relevant for immune targeting,” Jaffee said. ‘I want what Jimmy Carter had’: Patients clamor for the president’s cancer drug When neoantigens are found throughout a tumor, patients have the best shot at benefitting from immunotherapy drugs like Keytruda and Yervoy. Cancer Research UK/Phospho Biomedical Animation Related: The key to both — identifying patients likely to respond to the new immunotherapy drugs and producing tumor-attacking, individualized vaccines — lies in deciphering the crazy quilt of mutations a particular patient has.Only about one-fifth of cancer patients respond to immunotherapies like Keytruda, which is credited with helping Carter survive an advanced form of skin cancer. What makes “responders” different, previous studies in melanoma and lung cancer have suggested, is that they have a huge number of mutated genes producing molecules that find their way to the surface of the tumor cell. There, the aberrant molecules, known as neoantigens, stick out like pushpins in a corkboard.advertisement By Sharon Begley March 3, 2016 Reprints Turning your cancer against itselfVolume 90%Press shift question mark to access a list of keyboard shortcutsKeyboard ShortcutsEnabledDisabledPlay/PauseSPACEIncrease Volume↑Decrease Volume↓Seek Forward→Seek Backward←Captions On/OffcFullscreen/Exit FullscreenfMute/UnmutemSeek %0-9 facebook twitter Email Linkhttps://www.statnews.com/2016/03/03/cancer-immunotherapy-neoantigens/?jwsource=clCopied EmbedCopiedLive00:0002:0202:02  Personalized cancer vaccines rally the immune system to identify and kill cancerous cells based on genetic information from the patient’s own tumors. Alex Hogan and Hyacinth Empinado/STAT Because those neoantigens are newcomers, the immune system should recognize them as foreign and attack, destroying the cancer cell — which is where drugs like Merck’s Keytruda come in. They lift molecular blockades that tumors use to keep the immune system’s T cells out. As a result, T cells charge in and destroy the tumor.center_img Senior Writer, Science and Discovery (1956-2021) Sharon covered science and discovery. [email protected] Related: Watch: Turning your cancer against itself For cancer patients, the promise of new immune-modulating drugs like the one that apparently helped former President Jimmy Carter comes with a sobering downside: very few get any benefit from them.But if a new study published on Thursday is right, physicians might be able to figure out which patients those are, sparing others an expensive but useless treatment.The research also offers clues for how to make a promising but unproven treatment, personalized cancer vaccines, more likely to succeed.advertisement In the LabThe newest cancer therapies don’t work on everyone. Now, doctors have a clue why @sxbegle Tags cancercancer vaccinesKeytrudalast_img read more

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Letter to the Editor – Essential services

first_img At a time when older adults are even more isolated, lonely and medically vulnerable than usual, it is unconscionable to cut the critical funding that will help address these important issues. Darrell Goode says: ATF joins probe of LA blast that injured 12 firefighters1 in 5 Los Angeles County residents out of work, new report saysYou Might Also LikeFeaturedNewsBobadilla rejects Santa Monica City Manager positionMatthew Hall6 hours agoColumnsOpinionYour Column HereBring Back Library ServicesGuest Author12 hours agoNewsCouncil picks new City ManagerBrennon Dixson17 hours agoFeaturedNewsProtesting parents and Snapchat remain in disagreement over child protection policiesClara Harter17 hours agoFeaturedNewsDowntown grocery to become mixed use developmenteditor17 hours agoNewsBruised but unbowed, meme stock investors are back for moreAssociated Press17 hours ago I have no doubt that the City leadership is pondering the concern of Dr White in this article as well as other items before the leadership. I used the word item as this is how concerns are listed on agendas. However, sometimes items like those concerns here have to an require special attention as we all know there are human lives at stake, and so is our humanity depending how these issues are resolved in difficult times. Inanimate items vs. our human needs items commands the leadership to laser in on the human needs with balance so that when look back at what we have done we can look at ourselves to know we acted with compassion for others given we do not walk in their shoes.Respectfully,Darrell GoodeNAACP May 19, 2020 at 1:07 PM HomeOpinionColumnsLetter to the Editor – Essential services May. 19, 2020 at 6:00 amColumnsFeaturedHealthletterNewsNon ProfitsLetter to the Editor – Essential servicesGuest Author1 year agohuman services grants programletter to the editorwise & healthy aging Editor:As a long-time resident of Santa Monica and the retired head of a Santa Monica non-profit (Center for Healthy Aging), I want to voice my concerns about the proposed cut to the City of Santa Monica Human Services Grants Program. I am especially concerned about senior services provided by WISE &Healthy Aging but, also, the other non-profit organizations that serve the City’s vulnerable residents. An across-the-board budget cut will do harm that may not soon be resolved.While I understand the need to respond to the current economic and public health crisis, this is hardly the time to decrease services that contribute so significantly to the health and well-being of a highly at-risk population like the elderly. Specifically, for WISE & Healthy Aging alone, the funding cut would impact six programs: Adult Day Care, Care Management, Congregate Meals, Oasis, Transportation and Peer Counseling. These are ESSENTIAL services!The fact that the current funding cycle is no different from the previous four-year cycle plus the addition of the required 25% match, puts this organization—and the other Santa Monica non-profits—in an extremely difficult position. The negative impact of this budget cut on WISE & Healthy Aging and the other non-profit agencies and their clients, far outweighs the savings to the City. Surely there are other available strategies than reducing the FY2020-21 funding of the Human Service Grants Program for those in need.I happen to know that seniors attempted to contact the City Council about this cut, but many do not have computers and, with the Public Library closed, did not have access to any. Attempts to call City Hall on the afternoon of the Council meeting resulted in being put on hold so long they eventually hung up. Since Council Members are sheltered at home, it’s unlikely that many letters reached them.At a time when many people are scared, confused, isolated, lonely, in need of health and mental health care, and all the attention possible in this environment of separation, let’s not decrease the ability to provide assistance to them. Keep the FY2020-21 Human Services Grants Program as it is and utilize the time to work with the Santa Monica non-profit community to develop a viable plan for the future.Sincerely,Monika White, PhDSanta MonicaTags :human services grants programletter to the editorwise & healthy agingshare on Facebookshare on Twittershow 2 commentscenter_img 2 Comments Sandy Van says: May 19, 2020 at 8:53 PM Comments are closed.last_img read more

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Digital Radios Tested for High-Rise Crises

first_imgLangford has called the digital radio system, announced in 2006, the “biggest upgrade in 25 years” to fire communications. “We really wanted to get the users’ point of view,” outgoing Fire Commissioner Ray Orozco said of the decision to involve fire personnel. A six-week test — put off until the city could reinforce or rebuild decades-old radio towers to handle heavy new equipment — began this week to work out the kinks in the Motorola system. CHICAGO — After a lengthy delay that kept 2,100 portable radios in mothballs, the Chicago Fire Department is finally making the switch to a $22 million digital radio system designed to prevent a repeat of communications breakdowns at a deadly Loop high-rise fire. Six teams of technicians and firefighters will conduct “on-the-street driving exercises” and “in-building testing” at dozens of public and private sites to make certain the shift from an analog radio system to digital would not compromise public safety. The Motorola system will have more frequencies to handle heavy radio traffic. Some channels will be “encrypted” for security. And communication will be uninterrupted, even in high-rise buildings where service is notoriously sporadic. After evaluating 24 antenna sites, Motorola recommended that seven locations needed work — everything from shortening or strengthening towers and removing unused antennas to installing air-conditioning for digital equipment. Fire Department spokesman Larry Langford refused to say when the new system would “go live.” It depends on how smoothly the testing goes. Police officers and firefighters will be able to communicate directly, instead of relying on the cumbersome process of “console patching” by 911 center dispatchers. Firefighters and paramedics will use the same hand-held radios for the first time, instead of carrying two different radios to communicate directly. An eighth tower — at 31st and Sacramento — was 50 years old and needed to be rebuilt. It was torn down and replaced on the same site. With at least six fire ground frequencies instead of two, the new system should go a long way toward eliminating problems that plagued rescue efforts at the October 2003 fire at 69 W. Washington, when six people died after being trapped in a stairwell by locking doors.last_img read more

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Chart supplies nitrogen facility in Scotland

first_imgGet instant access to must-read content today!To access hundreds of features, subscribe today! At a time when the world is forced to go digital more than ever before just to stay connected, discover the in-depth content our subscribers receive every month by subscribing to gasworld.Don’t just stay connected, stay at the forefront – join gasworld and become a subscriber to access all of our must-read content online from just $270. Subscribelast_img

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B: Bouygues vs Dahl-Jenson

first_imgGet your free guest access  SIGN UP TODAY Stay at the forefront of thought leadership with news and analysis from award-winning journalists. Enjoy company features, CEO interviews, architectural reviews, technical project know-how and the latest innovations.Limited access to building.co.ukBreaking industry news as it happensBreaking, daily and weekly e-newsletters To continue enjoying Building.co.uk, sign up for free guest accessExisting subscriber? LOGIN Subscribe now for unlimited access Subscribe to Building today and you will benefit from:Unlimited access to all stories including expert analysis and comment from industry leadersOur league tables, cost models and economics dataOur online archive of over 10,000 articlesBuilding magazine digital editionsBuilding magazine print editionsPrinted/digital supplementsSubscribe now for unlimited access.View our subscription options and join our communitylast_img read more

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News in Brief

first_imgEIB is lending €40m to Poland’s rail infrastructure manager PKP PLK to fund upgrading of track and platforms at Siedlce, Lukow and Miedzyrzec Podlaski and signalling modernisation on 78 km between Siedlce and Biala Podlaska. By the end of 2015 line speeds will be raised to 160 km/h for passenger trains and 120 km/h for freight. Transport authorities in Thüringen and Niedersachsen have selected incumbent DB Regio to operate Dieselnetz Niedersachsen-Südost services totalling around 3·7 million train-km/year for 15 years from December 2014. HSH Nordbank is lead arranger for the financing of the UK’s £1·6bn Thameslink train procurement PPP, committing 7·5% of the commercial term loan financing. On July 5 the national railways of Russia, Slovakia, Austria and Ukraine agreed that their Breitspur Planungsgesellschaft joint venture would call tenders shortly for a detailed technical and environmental study into the planned Košice – Wien 1 520 mm gauge line. The German Land of Thüringen is to directly award incumbent Harzer Schmalspurbahnen the contract to operate Nordhausen – Ilfeld local services between March 2015 and December 2020. The European Commission has begun public consultation on ‘Effective Reduction of Noise Generated by Rail Freight Wagons in the European Union’, seeking views on the extent of the problem, assessment of existing measures, and the relevance and impact of proposed options. RFF has shortlisted four bidders for a contract to design, build, finance and maintain the Montpellier-Sud de France station due to open at the end of 2017 with the Nîmes – Montpellier bypass. A preferred bidder is due to be selected during the second quarter of 2014 for contract signature to follow in the summer of that year.last_img read more

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