T THE NEWDAWN OF immunotherapy afrontline cancer treatment. globe for abreakthrough that could make Steven Rosenbergmadeheadlinesaround the 16 science advanced during the20th dormant for decades,but asbiomedical technology ofradiotherapy. surgical techniquesandtheemerging toxins, but thiswassoonoutpaced bynew prototype treatment, knownasColey’s of theircancer. Coley developed a infections, andthesubsequent remission their immune response tothose bacterial infections incancer patients, The promise ofimmunotherapy lay SCIENTIST THE BIOMEDICAL established alinkbetween surgeon WilliamColey, who the pioneeringwork ofUS dates backtothe1890sand diseases suchascancer, defence mechanismtofight or modifyingthebody’s own he ideaofimmunotherapy, One-to-one OPINION

cancer hadgone,”says Steven. “He had without treatment. “All aspectsofhis patient whose tumourshasdisappeared career, when hemetayoung hadstartedearly inhis built onthisdiscovery. Hisinterest in Research, wasinvolved inthework that Cancer Institute (NCI) Center for Cancer at theUSNationalnow ChiefofSurgery Steven Rosenberg, thenayoung surgeon, Miraculous event specific threats. that adaptthebody’s immune response to known asTcells, orthewhite blood cells cultures ofTlymphocytes –otherwise ofhowtoproducediscovery invitro breakthrough camein1976with the century, it begantoreawaken. Akey

still alive today. She responded tothetreatment andis 67th patient afarhigherdoseofTcells. eluded them,but in1984theygave their them into patients. Initially, success and, inaseriesofearly trials,injected isolated varioustypesofimmune cells use themtodevelop acancer treatment.” that were attacking thecancer andthen cancer. Thisledustoidentify thecells recognise what wasdifferent about the there hadtobelymphocytes that could somewhere inthebody ofthepatient of billionslymphocytes,” hesays, “and immune system.“Thebody hashundreds to beburiedsomewhere inthepatient’s medicine –aspontaneous regression.” undergone oneofthemostrare events in metastic breast cancer who hadfailedto treatment for cancer. see immunotherapy become afrontline that suggestsabreakthrough that could clinical trial,published inNature Medicine, results, but it’s the outcome oftheirlatest lab. Thishasyieldedincreasingly positive and growing thembythebillionsin extracting Tcells from apatient’s body The key wastoperfect thetechniqueof Frontline treatment? Steven andhiscolleagues subsequently Steven felt theexplanation for thishad Their subjectwasapatient with STEVEN ROSENBERG

lymphomas. and sarcomas patients with cancer in of metastatic regressions have seen Recent studies metastatic remissions inpatientswith resulted incomplete immunotherapy have Studies ofcelltransfer advanced cancer therapies forpatientswith andgene Developed thefirsteffective Massachusetts Brigham HospitalinBoston, atthePeterBent Residency trainingin PhD inBiophysicsat Johns HopkinsUniversity, BA andMDdegreesat in Bethesda,Maryland National CancerInstitute Chief ofsurgeryatthe

IMAGES: SHUTTERSTOCK/NATIONAL CANCER INSTITUTE and immunotherapies, attacking the to allknownchemotherapies refractory Her cancer isnowinfullregression. response againstherindividual tumours. to create amuch more powerful immune inject thembackinto thepatient inorder TILs insufficient numbersinthelaband proteins. Thejobwasthentogrow these recognised oneormore ofhermutated tested theTILstopickout thosethat found 62different mutations. Next, they normal tissueandhertumours.They sequencing DNA andRNA from her patient’s uniquecell mutations by specifically target tumour cell mutations. patient, which, astheirnamesuggests, infiltrating lymphocytes (TILs)from the Steven andhisteamusedtumour- Targeting tumours lower levels ofmutations. ovarian, andbreast cancers, andhave the liningoforgans, suchasstomach, less effective with cancers that startin lung andbladder cancers, but hasbeen levels ofmutations, suchasmelanoma, successfully treated cancers with high . Thishas treatment ofmany typesofcancer”. sense ablueprint we canusefor the mutations, notoncancer type,it isina immunotherapy isdependent on because thisnewapproach to recognised bytheimmune system.But mutations present inacancer that are “a high-throughput methodtoidentify hormonal treatment. respond toallprevious chemotherapyand “For multiple cancer typesthat are Their firststepwastoidentify the It amounts toamodified form of Steven describeshisnewtechniqueas Pre-treatment 14 Months years aftertreatment.” on allavailable studiestwo-and-a-half cancer patient isnowcancer-free based regressions,” says Steven. “Thisbreast can result indramatic durable unique mutations inapatient’s cancer a personalised disease. towards toapersonalisedtreatment for the process have taken agiant leap complexities canbeovercome, andin have shownthat its inherent biological immunotherapy, Steven andhisteam Coley firstsuggestedtheideaof todevelop thiscommercially.”to try least three companies that are working change isneededandInowknowofat think thisisnotpractical.Iadrastic patient may beneeded.Many oncologists common cancers. Auniquedrugfor each tomakenecessary progress intreating personalised treatments are likely tobe paradigm for cancer therapy. Highly the way cancer istreated: “We needanew other patient.” the patient’s cancer andnotshared byany recognised mutations 196were uniqueto cancer, andthat ofthe197immunogenic lymphocytes reactive againsttheirown common epithelial cancers have T shown that about 80%ofpatients with of Cancer Research meetings,andhave (pictured) at two AmericanAssociation solid cancers. Ihave showed theslides immunotherapies for patients with the opportunities for findingeffective “This approach holds thebest the way forward for immunotherapy: It’s anoutcome that hehopeswillpoint Way forward Almost 130years after William Steven feels thisinsight shouldchange One-to-one OPINION somatic mutations lymphocytes targeting autologous Left. ACTusing

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