Car­los-Fil­ipe Pereira

Empow­er­ing Can­cer Immunother­a­py with Cel­lu­lar Reprogramming

Abstract

Immunother­a­py leads to long-term sur­vival of can­cer patients, yet gen­er­al­ized suc­cess has been ham­pered by insuf­fi­cient anti­gen pre­sen­ta­tion and exclu­sion of immuno­genic cells from the tumor microen­vi­ron­ment. We have devel­oped an approach to repro­gram tumor cells in vivo by ade­n­ovi­ral deliv­ery of the tran­scrip­tion fac­tors PU.1, IRF8, and BATF3, which enabled them to present anti­gens as type 1 con­ven­tion­al den­drit­ic cells. 

Repro­grammed tumor cells remod­eled their tumor microen­vi­ron­ment, recruit­ed, and expand­ed poly­clon­al cyto­tox­ic T cells, induced com­plete tumor regres­sions, and estab­lished long-term sys­temic immu­ni­ty in dif­fer­ent mouse melanoma mod­els. In human tumor spher­oids and xenografts, repro­gram­ming to immuno­genic den­drit­ic-like cells pro­gressed inde­pen­dent­ly of immuno­sup­pres­sion, which usu­al­ly lim­its immunother­a­py. Our stud­ies paves the way for first-in-human tri­als and oth­er appli­ca­tions of immune cell repro­gram­ming in vivo.

Biography/​Link

Car­los-Fil­ipe Pereira, Ph.D. is a Pro­fes­sor of Mol­e­c­u­lar Med­i­cine in the Fac­ul­ty of Med­i­cine at Lund Uni­ver­si­ty in Swe­den. Dr. Pereira is rec­og­nized for his work at the inter­face of cel­lu­lar repro­gram­ming and immunol­o­gy and for fos­ter­ing devel­op­ment of repro­gram­ming-based immunotherapies.

For the last 20 years he has con­tributed to the fields of cel­lu­lar repro­gram­ming and hematopoi­et­ic spec­i­fi­ca­tion. Dr. Pereira received his Ph.D. at Impe­r­i­al Col­lege Lon­don where he estab­lished cell fusion and het­erokaryons to study mech­a­nisms of repro­gram­ming towards pluripo­ten­cy. Dur­ing his post­doc­tor­al train­ing at the Icahn School of Med­i­cine at Mount Sinai in New York, he brought cel­lu­lar repro­gram­ming con­cepts to hematopoei­sis for the first time. Dr. Pereira start­ed his inde­pen­dent group at Lund Uni­ver­si­ty in 2017 and has uncov­ered new mech­a­nisms under­ly­ing hematopoi­et­ic repro­gram­ming and defin­i­tive hematopoiesis spec­i­fi­ca­tion. He pio­neered cel­lu­lar repro­gram­ming approach­es in immunol­o­gy by induc­ing den­drit­ic cells from fibrob­lasts and can­cer cells. This con­cep­tu­al shift opened excit­ing oppor­tu­ni­ties to merge cel­lu­lar repro­gram­ming and can­cer immunother­a­py. Dr. Pereira co-found­ed Asgard Ther­a­peu­tics, which received invest­ment from lead­ing Euro­pean VCs to trans­late in vivo den­drit­ic cell repro­gram­ming to ben­e­fit can­cer patients.

For his sci­en­tif­ic accom­plish­ments and inno­va­tion efforts, he received sev­er­al notable sci­en­tif­ic awards, includ­ing ERC Con­sol­ida­tor and Proof-of-Con­cept Grants, the Novo Nordisk Foun­da­tion Dis­tin­guished Inno­va­tor Grant and the entre­pre­neur­ship award from Mount Sinai-KiiLN. Dr. Pereira is a fel­low of the Swedish Wal­len­berg pro­gram in Mol­e­c­u­lar Med­i­cine and Edi­tor-in-Chief of the jour­nal Cel­lu­lar Repro­gram­ming. He was also award­ed the pres­ti­gious Swedish Fern­ström Prize and a medal of mer­it from his home­town in Portugal.

pereiral​ab​.com

https://​www​.stem​cell​cen​ter​.lu​.se/​r​e​s​e​a​r​c​h​-​g​r​o​u​p​s​/​p​e​r​e​ira