Cancer nanovaccines may revolutionize cancer treatment

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Cancer nanovaccines may revolutionize cancer treatment

Friday, 30.08.2019

In a study just published in Nature Nanotechnology led by Prof. Helena F. Florindo, from the Faculty of Pharmacy, University of Lisbon, and Prof. Ronit Satchi-Fainaro, from the Sackler Faculty of Medicine, Tel Aviv University, describe that the combination of these nanovaccines with therapies available in the clinic. These nanovaccines re-educated host immune system, enabling the identification of protein markers expressed at the surface of tumors, specifically melanoma, which resulted in a remarkable tumor inhibition and prolonged survival in preclinical models of this disease.


Authors and Affiliations:

João Conniot,1,2¥ Anna Scomparin, 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,Ronit Satchi-Fainaro,1* Helena F Florindo,2*

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 

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: From left to right: Helena F. Florindo (Faculdade de Farmácia da Universidade de Lisboa (FFULisboa)), João Conniot (FFULisboa), Ronit Satchi-Fainaro (Univ. TLV) and Anna Scoomparin (Univ. TLV).



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.


Journal: Nature Nanotechnology