The sci­ence of im­munother­apy,

Pittsburgh Post-Gazette - - Front Page - By David Tem­ple­ton David Tem­ple­ton: dtem­ple­ton@post-gazette.com or 412-263-1578. Twit­ter: @tem­ple­toons.

Ma­nip­u­lat­ing the im­mune sys­tem to fight dis­ease has been the long­stand­ing goal of med­i­cal sci­ence.

Then, in 2010, Carl H. June and his Uni­ver­sity of Penn­syl­va­nia School of Medicine re­search team en­gi­neered im­mune cells to suc­cess­fully treat two pa­tients with chronic lym­pho­cytic leukemia who achieved full re­mis­sion with par­tial re­mis­sion for a third pa­tient. The world took no­tice and cheered. And that suc­cess helped to fur­ther in­spire im­munother­apy re­search world­wide.

It makes good sense. The im­mune sys­tem is our nat­u­ral method of heal­ing. So bol­ster the im­mune sys­tem — the T cells — to treat can­cer. De­sen­si­tize them to treat au­toim­mune dis­eases. Pre­vent them from re­ject­ing trans­planted or­gans. Make bet­ter vac­cines to more uni­ver­sally fight vi­ral and bac­te­rial in­fec­tions.

Then there’s in­flam­ma­tion — chronic over-ac­ti­va­tion of the im­mune sys­tem that ad­versely af­fects health on mul­ti­ple fronts and ap­par­ently is a fac­tor in ag­ing.

All of this ex­plains the forces that led to cre­ation of the UPMC Im­mune Trans­plant and Ther­apy Cen­ter in Bloom­field to de­velop treat­ments use­ful to fight can­cer, au­toim­mune dis­ease, trans­plant re­jec­tion and ag­ing.

Typ­i­cally, aca­demic re­search cen­ters hand off their drugs to phar­ma­ceu­ti­cal com­pa­nies to test, get ap­proval and mar­ket. But the cen­ter will per­form clin­i­cal tri­als then go through the ex­pen­sive and of­ten lengthy ap­proval process by the U.S. Food and Drug Ad­min­is­tra­tion be­fore mar­ket­ing and dis­tribut­ing new drug prod­ucts world­wide.

UPMC of­fi­cials call the ver­ti­cal con­cept as “bench to bed­side” — drug de­vel­op­ment to mar­ket­place.

“It turns out that the im­mune sys­tem has an im­pact on so many as­pects of hu­man health, and more than we orig­i­nally thought,” said Mark Shlom­chik, a UPMC en­dowed pro­fes­sor of im­munol­ogy and chair of the Pitt School of Medicine’s Depart­ment of Im­munol­ogy. “Many peo­ple un­der­stand the im­mune sys­tem fight­ing vi­ral or bac­te­rial in­fec­tions, ex­plain­ing our nat­u­ral abil­ity to kill germs. Peo­ple also are aware of how vac­cines work by us­ing non­in­fec­tious forms [of the virus or bac­te­ria] to teach the im­mune sys­tem, which has a mem­ory. Then when an in­fec­tion comes along, it can re­sist it.”

But with au­toim­mune dis­eases, he said, the im­mune sys­tem is overzeal­ous and starts at­tack­ing healthy cells and tis­sue, be they in­sulin­pro­duc­ing beta cells, joint tis­sue in rheuma­toid arthri­tis or the myelin sheath around nerve cells in mul­ti­ple scle­ro­sis, among many oth­ers. Also, in pro­tect­ing trans­planted or­gans, the key is prevent­ing the im­mune sys­tem per­ma­nently from at­tack­ing the donor or­gan.

“Some­times when the im­mune sys­tem is too charged up, you want to put the brakes on,” Dr. Shlom­chik said.

Then there’s can­cer, where the tu­mor has many ways of win­ning the bat­tle against the im­mune sys­tem, ei­ther by grow­ing faster than T cells can re­act, or hid­ing fro­mor de­ac­ti­vat­ing them.

“In the last sev­eral years, there have been some break­throughs where we’ve learned to give the ad­van­tage back to the im­mune sys­tem, and take the brakes off, and now there are sev­eral drugs ap­proved by the FDA to treat me­lanoma, lung and kid­ney can­cers,” he said. “This is like Jimmy Carter’s [me­lanoma that spread to his liver and brain]. He was put on a drug and the tu­mor nat­u­rally re­gressed. It in­volves tak­ing the brakes off the im­mune sys­tem, and the im­mune sys­tem nat­u­rally de­stroys the tu­mor.”

These drugs known as check­point in­hibitors pre­vent degra­da­tion of im­mune cells at cer­tain steps dur­ing the im­mune re­sponse. For now, how­ever, the drugs work only 20 per­cent to 40 per­cent of the time, which means suc­cess to many pa­tients but leaves many oth­ers with­out al­ter­na­tive treat­ments.

“Var­i­ous re­searchers at Pitt are try­ing to turn T cells back on. We cap­ture T cells in a tu­mor that are do­ing their job but not win­ning the bat­tle,” Dr. Shlom­chik said. “They are re­gen­er­ated [in a lab­o­ra­tory] up to a thou­sand­fold and re-en­er­gized.” Then they are rein­tro­duced.

“From a small band of sol­diers, we are mak­ing an army that can kill the tu­mor,” he said.

Ewa Krawczyk/Na­tional In­sti­tutes of Health

A flu­o­res­cence-col­ored mi­cro­scope im­age from the Na­tional In­sti­tutes of Health shows a cul­ture of hu­man breast can­cer cells.

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