Associação Portuguesa de Investigação em Cancro
Vacina à escala nano que pode revolucionar o tratamento do cancro
Vacina à escala nano que pode revolucionar o tratamento do cancro
Um estudo publicado na revista britânica Nature Nanotechnology, liderado pela investigadora Helena Florindo, da Faculdade de Farmácia da Universidade de Lisboa, e pela investigadora Ronit Satchi-Fainaro da Universidade de Tel Aviv, apresenta os resultados da combinação de uma vacina anti-tumoral com outros tratamentos já utilizados em células que bloqueiam a resposta imunológica do nosso corpo contra células cancerígenas. A vacina desenvolvida tem a capacidade de "re-educar" o sistema imunitário conferindo-lhe a capacidade de reconhecer proteínas produzidas apenas por tumores, em particular melanomas, o que conduz a uma notável inibição do crescimento do tumor, bem como a um aumento do tempo de vida dos doentes.
Autores e Afiliações:
João Conniot,1,2¥ Anna Scomparin,1¥ Carina Peres,2 Eilam Yeini,1 Sabina Pozzi,1 Ana I Matos,2 Ron Kleiner,1 Liane Moura,2 Eva Zupančič,2,3 Ana S Viana,4 Hila Doron,5 Pedro MP Góis,2 Neta Erez,5 Steffen Jung,3 Ronit Satchi-Fainaro,1* Helena F Florindo,2*
1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
3 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
4 Center of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Lisbon, Portugal, Portugal
5 Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
¥These authors equally contributed to this work
*Corresponding authors
Foto: Da esquerda para a direita: Helena F. Florindo (Faculdade de Farmácia da Universidade de Lisboa (FFULisboa)), João Conniot (FFULisboa), Ronit Satchi-Fainaro (Univ. TLV) and Anna Scoomparin (Univ. TLV).
Abstract:
Low response rate, acquired resistance, and severe side effects have limited the clinical outcomes of immune checkpoint therapy.We hypothesized that the combination of cancer nano-vaccines with anti-PD-1 for immunosuppression blockade, and the agonist antibody anti-OX40 for effector T cell stimulation, expansion, and survival, could potentiate the efficacy of melanoma therapy. We developed dendritic cell-targeted mannose-grafted poly(lactic-co-glycolic acid) nano-vaccines containing melan-A/MART-1 peptides and immune potentiators. Both prophylactic and therapeutic combination regimens of mannosylated nano-vaccines with anti-PD-1/anti-OX40(aPD-1/aOX40) demonstrated synergism, stimulating T cell infiltration into tumors at early stages of the treatment. The prophylactic regimen inhibited tumor growth to a greater extent compared to the aPD-1/aOX40 alone, however, treatment at the therapeutic regimen did not result in enhanced inhibition of tumor growth compared to the aPD-1/aOX40 alone. An increased infiltration of myeloid-derived suppressor cells (MDSC) was observed in tumors of animals treated at the therapeutic regimen with the combination of mannosylated nano-vaccines with aPD-1/aOX40. In fact, when combining ibrutinib, an MDSC-inhibitor, with the double therapy mannosylated nano-vaccines and aPD-1/aOX40, a remarkable tumor remission and prolonged survival was achieved in treated melanoma-bearing mice. The synergy between the mannosylated nano-vaccines, ibrutinib and aPD-1/aOX40 provides essential insights to devise alternative regimens and combination therapies to improve the efficacy of immune checkpoint modulators in solid tumors, by regulating the endogenous immune response.
Revista: Nature Nanotechnology
