Cells re­pro­grammed to fight cancer

Windsor Star - - FRONT PAGE -

Ken She­fve­land’s body was swollen with cancer, treat­ments fail­ing un­til doc­tors re­moved some of his im­mune cells, en­gi­neered them into cancer as­sas­sins and un­leashed them into his blood­stream.

Im­mune ther­apy is the hottest trend in cancer care and this is its next fron­tier — cre­at­ing “liv­ing drugs” that grow in­side the body into an army that seeks and de­stroys tu­mours.

She­fve­land said “the cancer was just melt­ing away.” A month later doc­tors at the Fred Hutchin­son Cancer Re­search Cen­ter couldn’t find any signs of lym­phoma in the Van­cou­ver, Wash., man’s body.

“To­day I find out I’m in full re­mis­sion — how won­der­ful is that?” said She­fve­land.

This ex­per­i­men­tal ther­apy marks an en­tirely new way to treat cancer — if sci­en­tists can make it work, safely. Early stage stud­ies are stir­ring hope as one-time in­fu­sions of su­per­charged im­mune cells help a re­mark­able num­ber of pa­tients with in­tractable leukemia or lym­phoma.

“It shows the un­be­liev­able power of your im­mune sys­tem,” said Dr. David Maloney, Fred Hutch’s med­i­cal direc­tor for cel­lu­lar im­munother­apy who treated She­fve­land with a type called CAR-T cells.

“We’re talk­ing, really, pa­tients who have no other op­tions, and we’re see­ing tu­mours and leukemias dis­ap­pear over weeks,” added im­munother­apy sci­en­tific direc­tor Dr. Stan­ley Rid­dell. But “there’s still lots to learn.”

T cells are key im­mune sys­tem sol­diers. But cancer can be hard for them to spot, and can put the brakes on an im­mune at­tack. To­day’s pop­u­lar im­munother­apy drugs called “check­point in­hibitors” re­lease one brake so nearby T cells can strike. The new cel­lu­lar im­munother­apy ap­proach aims to be more po­tent: Give pa­tients stronger T cells to be­gin with.

Cur­rently avail­able only in stud­ies at ma­jor cancer cen­tres, the first CAR-T cell ther­a­pies for a few blood cancers could hit the mar­ket later this year. The U.S. Food and Drug Ad­min­is­tra­tion is eval­u­at­ing two dif­fer­ent ver­sions.

CAR-T ther­apy “feels very much like it’s ready for prime time” for ad­vanced blood cancers, said Dr. Nick Hain­ing of the DanaFar­ber Cancer In­sti­tute and Broad In­sti­tute of MIT and Har­vard, who isn’t in­volved in the devel­op­ment.

Now sci­en­tists are tack­ling a tougher next step, what Hain­ing calls “the acid test”: Mak­ing T cells tar­get far more com­mon cancers — solid tu­mours like lung, breast or brain cancer. Cancer kills about 600,000 Amer­i­cans a year, and ap­prox­i­mately 79,000 in Canada.

Sci­en­tists still are un­rav­el­ling why th­ese liv­ing cancer drugs work for some peo­ple and not others.

Doc­tors must learn to man­age po­ten­tially life-threat­en­ing side­ef­fects from an over­stim­u­lated im­mune sys­tem. Also con­cern­ing is a small num­ber of deaths from brain swelling, an un­ex­plained com­pli­ca­tion that forced an­other com­pany, Juno Ther­a­peu­tics, to halt devel­op­ment of one CAR-T in its pipe­line; Kite recently re­ported a death, too.

“It’s a Model A Ford and we need a Lam­borgh­ini,” said CAR-T re­searcher Dr. Re­nier Bren­t­jens of New York’s Memo­rial Sloan Ket­ter­ing Cancer Cen­ter, which, like Hutch, has a part­ner­ship with Juno.

At a recently opened Seat­tle im­munother­apy clinic, sci­en­tists are tak­ing newly de­signed T cells from the lab to the pa­tient and back again to tease out what works best.

“We can es­sen­tially make a cell do things it wasn’t pro­grammed to do nat­u­rally,” ex­plained im­munol­ogy chief Dr. Philip Green­berg. “Your imag­i­na­tion can run wild with how you can en­gi­neer cells to func­tion bet­ter.”

TWO LONG WEEKS TO BREW A DOSE

When leukemia pa­tient Claude Ban­nick en­tered a Hutch CAR-T study in 2014, nurses hooked him to a ma­chine that fil­tered out his white blood cells, including the T cells.

Tech­ni­cians raced his bag of cells to a fac­tory-like fa­cil­ity that’s kept so ster­ile they must pull on ger­mde­flect­ing suits, booties and masks just to en­ter. Then came 14 days of wait and worry, as his cells were re­pro­grammed.

Ban­nick, 67, says he “was al­most dead.” Chemo­ther­apy, ex­per­i­men­tal drugs, even a bone-mar­row trans­plant had failed, and “I was will­ing to try any­thing.”

WHAT’S THE DATA?

Small, early stud­ies in the U.S. made head­lines as 60 per cent to 90 per cent of pa­tients try­ing CAR-Ts as a last re­sort for leukemia or lym­phoma saw their cancer rapidly de­crease or even be­come un­de­tectable. Recently, Chi­nese re­searchers re­ported sim­i­lar early find­ings as 33 of 35 pa­tients with an­other blood cancer, mul­ti­ple myeloma, reached some de­gree of re­mis­sion within two months.

Too few peo­ple have been stud­ied so far to know how long such re­sponses will last. A re­cent re­view re­ported up to half of leukemia and lym­phoma pa­tients may re­lapse.

There are long-term survivors including Doug Ol­son who in 2010 re­ceived the Univer­sity of Penn­syl­va­nia’s CAR-T ver­sion for leukemia.

Ban­nick, the Hutch pa­tient treated in 2014, had some lin­ger­ing side­ef­fects but says CAR-T is “giv­ing me a sec­ond life.”

SCARY SIDE-EF­FECTS

As CAR-T cells swarm the cancer, an im­mune over­re­ac­tion called “cy­tokine re­lease syn­drome” can trig­ger high fevers and plum­met­ing blood pres­sure and in se­vere cases or­gan dam­age. Some pa­tients also ex­pe­ri­ence con­fu­sion, hal­lu­ci­na­tions or other neu­ro­logic symp­toms.

FIGHT­ING SOLID TU­MOURS WILL BE HARDER

CAR-Ts cause col­lat­eral dam­age, killing some healthy white blood cells, called B cells, along with can­cer­ous ones be­cause both har­bour the same marker. Find­ing the right tar­get to kill solid tu­mours,but not healthy or­gan tis­sue, will be even more com­pli­cated.

“This is the hope of any cancer pa­tient, that if you stay in the game long enough, the next treat­ment’s go­ing to be just around the cor­ner,” said She­fve­land.

Doc­tors re­pro­gram pa­tients’ cells to turn them into cancer fight­ers, Lau­ran Neer­gaard writes.

PHO­TOS: ELAINE THOMP­SON/THE AS­SO­CI­ATED PRESS

Ken She­fve­land has had some of his im­mune cells re­pro­grammed into an army of “liv­ing drugs” to bet­ter de­stroy his cancer.

Cell pro­duc­tion as­so­ciate Her­ley Beyene, left, places con­tain­ers of im­mune cells in a cen­trifuge at the Fred Hutchin­son Cancer Re­search Cen­ter in Seat­tle. Re­searchers are ge­net­i­cally re­pro­gram­ming pa­tients’ im­mune cells to cre­ate “liv­ing drugs” that help fight cancer. Right: Re­search tech­ni­cian Ash­wini Balakr­ish­nan works in the im­munother­apy re­search lab at the cen­tre.

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