Us­ing the Im­mune Sys­tem to Fight Can­cer

Wellness Update - - Meet Our Doctors -

About a quar­ter of pa­tients with deadly can­cers had sig­nif­i­cant re­duc­tions of tu­mor size af­ter tak­ing a new an­ti­body drug, ac­cord­ing to re­sults of a large early-stage clin­i­cal trial con­ducted by sci­en­tists from Yale School of Medicine, Johns Hop­kins Univer­sity, Har­vard Univer­sity, Bris­tol-My­ers Squibb, and other ma­jor in­sti­tu­tions. The study ap­pears in the New Eng­land Jour­nal of Medicine. The find­ings are also be­ing pre­sented at the an­nual meet­ing of the Amer­i­can So­ci­ety of Clin­i­cal On­col­ogy. Nearly 300 pa­tients with ad­vanced melanoma, non-small cell lung can­cer, or re­nal cell can­cer whose can­cer pro­gressed af­ter re­ceiv­ing stan­dard treat­ments were given the drug, which boosts the im­mune sys­tem’s ca­pac­ity to fight can­cer. “This is the first agent that blocks the tu­mor’s abil­ity to fend off the can­cer-fight­ing cells of the im­mune sys­tem,” said se­nior au­thor Mario Sznol, M.D., pro­fes­sor of medicine at Yale School of Medicine and co-di­rec­tor of the melanoma pro­gram at Yale Can­cer Cen­ter. The study drug — BMS-936558 (MDX-1106, anti-PD-1), man­u­fac­tured by Bris­tol-My­ers Squibb — is an an­ti­body de­signed to block a protein known as “pro­grammed death-1” (PD-1), which is present on the sur­face of im­mune lym­pho­cyte cells (types of white blood cells) and in­hibits their func­tion. Ad­min­is­tra­tion of BMS-936558 is thought to re­store the func­tion of can­cer-fight­ing lym­pho­cytes. Anti-PD-1 was ad­min­is­tered to 296 pa­tients whose can­cer had grown de­spite stan­dard treat­ment. Tu­mor shrink­age of at least 30 per­cent was seen in 18 per­cent of the lung can­cer pa­tients, 28 per­cent of the melanoma pa­tients, and 27 per­cent of the re­nal-cell pa­tients. Over­all, anti-PD1 was gen­er­ally well tol­er­ated by pa­tients, although a few pa­tients devel­oped se­vere and some­times life-threat­en­ing side ef­fects. Re­searchers re­ported that pa­tients’ re­sponse to the drug tended to be lon­glast­ing, in some cases more than a year. Re­searchers were par­tic­u­larly in­trigued by the re­sponse of pa­tients with lung can­cer, a type of can­cer that many re­searchers thought would not be re­spon­sive to im­mune ther­a­pies. “I be­lieve we can ex­tend th­ese treat­ments to other types of can­cer, and have great hope to im­prove them fur­ther by com­bin­ing with other kinds of anti-can­cer drugs,” Sznol said. Co-au­thor Lieping Chen, M.D., pro­fes­sor of im­muno­bi­ol­ogy, medicine, and der­ma­tol­ogy at Yale School of Medicine and di­rec­tor of the can­cer im­munol­ogy pro­gram at Yale Can­cer Cen­ter, has made ma­jor con­tri­bu­tions to the dis­cov­er­ies of th­ese im­mune mol­e­cules, in­clud­ing the sup­pres­sive mech­a­nisms of PD-1 and its two lig­ands, PD-L1 and PD-L2. “We are now all con­vinced that our own im­mune sys­tem is very pow­er­ful if it is switched on in the right way. It is also par­tic­u­larly ex­cit­ing and re­ward­ing to see the dis­cov­er­ies made in the lab­o­ra­tory be­ing trans­lated into clin­i­cal tri­als,” Chen said. Co-au­thor Scott Get­tinger, M.D., as­so­ciate pro­fes­sor of medicine at Yale School of Medicine, who treated the most pa­tients with lung can­cer tak­ing part in the multi-cen­ter trial, is work­ing with Chen and other sci­en­tists at Yale to un­der­stand why some pa­tients re­spond and oth­ers didn’t re­spond to anti-PD1 treat­ment. “We have seen promis­ing re­sults in this study, with some dra­matic re­sponses in pa­tients that ap­pear to be long last­ing in most cases,” Get­tinger said. “Fur­ther­more, this ther­apy has been well tol­er­ated, markedly bet­ter than other avail­able sal­vage ther­a­pies that are as­so­ci­ated with low re­sponse rates.” -This in­for­ma­tion pro­vided courtesy of Yale Can­cer Cen­ter

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