Elec­tric jolt helps T-cells bat­tle can­cer

Santa Fe New Mexican - - NATION & WORLD - By Ben Guar­ino

A promis­ing new class of can­cer treat­ments re­cruits the cells in our blood to fight tu­mors, us­ing pow­er­ful gene-edit­ing tools to trans­form a type of white blood cell — called a T-cell — from an im­mune cell that nor­mally tar­gets bac­te­rial or fun­gal in­fec­tions into a liv­ing can­cer drug.

The ge­netic al­ter­ations could boost im­mune sys­tems to suc­cess­fully fight can­cers on their own. Re­searchers re­move T-cells from pa­tients and slip new genes into the cells. Af­ter clin­i­cians re­turn the mod­i­fied T-cells to pa­tients, the cells, like mi­cro­scopic blood­hounds, lead the im­mune sys­tem on the hunt for tu­mors.

“We’re liv­ing in an amaz­ing mo­ment in can­cer im­munother­a­pies,” said Alexan­der Mar­son, a mi­cro­bi­ol­ogy and im­munol­ogy pro­fes­sor at the Uni­ver­sity of Cal­i­for­nia, San Fran­cisco.

In 2017, the Food and Drug Ad­min­is­tra­tion be­gan ap­prov­ing ge­net­i­cally al­tered im­mune cells for small groups of pa­tients, such as those with ag­gres­sive non-Hodgkin lym­phoma or a rare form child­hood leukemia. Other ex­per­i­men­tal tri­als, in­volv­ing can­cers such as myeloma and melanoma, show en­cour­ag­ing re­sults.

But fur­ther de­vel­op­ments have been slowed, with a bot­tle­neck aris­ing not from red tape but de­mand. De­liv­ery sys­tems able to in­sert new genes into im­mune cells are in short sup­ply.

Dis­abled viruses, which in­ject genes into cells like a shot from a sy­ringe, are the cur­rent stan­dard. Just a few biotech­nol­ogy com­pa­nies, equipped with ex­pen­sive man­u­fac­tur­ing sys­tems, can pro­duce the vi­ral vec­tors. Wait times for new viruses can be as long as sev­eral years, as James Wil­son, who di­rects the gene ther­apy pro­gram at the Uni­ver­sity of Penn­syl­va­nia’s Perel­man School of Medicine, told the New York Times in Novem­ber.

Mar­son and his col­leagues have de­vel­oped a new, faster method to re­pro­gram T-cells, as they de­scribed Wednes­day in the journal Na­ture. Rather than re­ly­ing on viruses to de­liver the ge­netic pack­age, re­searchers jolted T-cells with elec­tric­ity. The shock re­laxed the mem­branes that sur­round the cells, mak­ing them re­cep­tive to new ge­netic ma­te­rial.

“It’s a turn­ing point,” said Vin­cenzo Cerun­dolo, di­rec­tor of the Hu­man Im­munol­ogy Unit at Ox­ford Uni­ver­sity, who was not in­volved with this study. “It is a game-changer in the field and I’m sure that this tech­nol­ogy has legs.” He pre­dicts cheaper ther­a­pies and much faster de­vel­op­ment times — as swiftly as a week, rather than the months re­quired to man­u­fac­ture a virus.

In the new re­search, Theodore Roth, a doc­toral stu­dent in Mar­son’s lab, per­formed thou­sands of ex­per­i­ments in quick suc­ces­sion to iden­tify the best way to zap new genes into T-cells.

The method’s ef­fi­ciency var­ied, de­pend­ing on the donor cells and the tar­geted genes. In cells from healthy vol­un­teers, the most suc­cess­ful group, the new genes in­te­grated with as many as 35 per­cent or 40 per­cent of cells.

Study co-au­thor Ke­van Herold, an en­docri­nol­o­gist and im­mu­nol­o­gist at Yale Uni­ver­sity, said it is too early to dis­cuss cost, ex­cept to note that the ther­a­pies are not in­ex­pen­sive.

Cur­rent costs for gene ther­apy can be as high as $1 mil­lion for rare dis­eases. Treat­ment for more com­mon dis­eases also can be ex­pen­sive, with bills run­ning in the six-fig­ures.

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