Af­ter a run of CT­LA-4 com­bo fail­ures, sci­en­tists spot­light a way to make it work — in se­lect pa­tients

CT­LA-4/PD-(L)1 com­bi­na­tions have been one of the El Do­ra­dos of on­col­o­gy, its promise for­ev­er be­hind that next hill but ap­par­ent­ly un­at­tain­able af­ter a se­ries of piv­otal clin­i­cal fail­ures. But re­searchers at New York’s Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter and the Tech­ni­cal Uni­ver­si­ty of Mu­nich think they may know how to fix what’s wrong and boost the dri­ve to next-gen can­cer com­bos.

In a pre­clin­i­cal an­i­mal re­search pro­gram, re­searchers found that with­in a cell, check­points re­ly on a spe­cif­ic mol­e­cule — RNA-sens­ing mol­e­cule RIG-I — to work. If that sounds fa­mil­iar, it’s be­cause it has al­ready been iden­ti­fied as a tar­get for boost­ing im­mune re­spons­es and was sub­ject to at least one Phase I/II tri­al. Pfiz­er in De­cem­ber al­lied it­self with Kine­ta with $15 mil­lion up­front and $505 mil­lion in po­ten­tial mile­stones to de­vel­op RIG-I im­munother­a­pies, and three years ago Mer­ck pur­chased Ger­man up­start Rigontec for $137 mil­lion up­front and over $400 mil­lion in po­ten­tial mile­stones for the same pur­pose.

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