A cou­ple of high-pro­file can­cer re­searchers at MD An­der­son backed by the Park­er In­sti­tute have been ex­plor­ing an ex­per­i­men­tal path­way that they be­lieve shows some re­al po­ten­tial in treat­ing pan­cre­at­ic can­cer. And the news could buoy de­vel­op­ers beaver­ing away at clin­i­cal de­vel­op­ment in this are­na of im­munother­a­py.

Pad­ma­nee Shar­ma along with her long­time col­lab­o­ra­tor, hus­band and No­bel lau­re­ate Jim Al­li­son ap­proached the is­sue by com­par­ing pan­cre­at­ic can­cer tu­mors against melanoma, where PD-1/L1 and CT­LA-4 check­point in­hibitors have showed some of their great­est suc­cess­es. Pan­cre­at­ic can­cer, though, has a small 5-year sur­vival rate, demon­strat­ing its re­sis­tance to the new check­point class of drugs now out on the mar­ket.

Shar­ma and Al­li­son’s team not­ed a sig­nif­i­cant­ly dif­fer­ent pro­file for each can­cer, with a much high­er lev­el of stro­ma in pan­cre­at­ic can­cer tu­mors that could be in­ter­fer­ing with ex­ist­ing check­points. The stro­ma — sup­port­ive cells — is lay­ered in­to pan­cre­at­ic can­cer.

“In melanoma, you have a large area of ma­lig­nant cells sur­round­ed by a thin lay­er of stro­ma,” not­ed Shar­ma. “With pan­cre­at­ic can­cer, it’s more like can­cer cells, stro­ma, can­cer cells, stro­ma ― blend­ed.”

The in­ves­ti­ga­tors al­so not­ed a high­er ex­pres­sion of VISTA — V-do­main Ig sup­pres­sor of T cell ac­ti­va­tion — in pan­cre­at­ic can­cer.

Al­li­son’s ob­ser­va­tion is that stro­ma may in turn keep T cells out of the pan­cre­at­ic can­cer tu­mors. The can­cer sci­en­tist won the No­bel prize in med­i­cine for his orig­i­nal work on the CT­LA-4 check­point, which opened the door to an im­mense amount of work glob­al­ly fol­low­ing it up with new ap­proach­es.

There are sev­er­al VISTA an­ti­bod­ies in the glob­al pipeline, they note. That group ev­i­dent­ly in­cludes Curis, a pen­ny stock mi­cro­cap which has a small mol­e­cule pro­gram that com­bines VISTA and PD-L1.

The goal now, the MD An­der­son pair sum up, is to see about start­ing work on some new check­point com­bos — per­haps match­ing CT­LA-4 and VISTA. Their work was fund­ed by Pan­cre­at­ic Can­cer Moon Shot, a grant from the Na­tion­al Can­cer In­sti­tute and the Park­er In­sti­tute for Can­cer Im­munother­a­py.

Im­age: Jim Al­li­son and Pad­ma­nee Shar­ma at the King’s din­ner for the No­bel Lau­re­ates. AP IM­AGES

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