Personalized combination nano-immunotherapy for robust induction and tumor infiltration of CD8+ T cells.

Biomaterials
Kyung Soo ParkJames J Moon

Abstract

Identification of tumor-specific mutations, called neoantigens, offers new exciting opportunities for personalized cancer immunotherapy. However, it remains challenging to achieve robust induction of neoantigen-specific T cells and drive their infiltration into the tumor microenvironment (TME). Here, we have developed a novel polyethyleneimine (PEI)-based personalized vaccine platform carrying neoantigen peptides and CpG adjuvants in a compact nanoparticle (NP) for their spatio-temporally concerted delivery. The NP vaccine significantly enhanced activation and antigen cross-presentation of dendritic cells, resulting in strong priming of neoantigen-specific CD8+ T cells with the frequency in the systemic circulation reaching as high as 23 ± 7% after a single subcutaneous administration. However, activated CD8+ T cells in circulation exhibited limited tumor infiltration, leading to poor anti-tumor efficacy. Notably, local administration of stimulator of interferon genes (STING) agonist promoted tumor infiltration of vaccine-primed CD8+ T cells, thereby overcoming one of the major challenges in achieving strong anti-tumor efficacy with cancer vaccination. The NP vaccination combined with STING agonist therapy eliminated tumors in ...Continue Reading

References

Mar 20, 2002·Cytokine & Growth Factor Reviews·Mario P Colombo, Giorgio Trinchieri
Feb 13, 2009·Advanced Drug Delivery Reviews·Jörg Vollmer, Arthur M Krieg
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael A CurranJames P Allison
Jan 13, 2012·Cancer Research·John C CastleUgur Sahin
Dec 22, 2012·The EMBO Journal·Bianca HeemskerkTon N M Schumacher
Jul 31, 2013·Immunity·Daniel S Chen, Ira Mellman
Feb 11, 2015·Current Opinion in Immunology·Evripidis LanitisGeorge Coukos
Apr 4, 2015·Science·Ton N Schumacher, Robert D Schreiber
Sep 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Leticia Corrales, Thomas F Gajewski
Dec 27, 2016·Nature Materials·Rui KuaiJames J Moon
Jan 24, 2017·Cell·Matthew H SpitzerEdgar G Engleman
Jul 6, 2017·Nature·Patrick A OttCatherine J Wu
Jul 14, 2017·British Journal of Cancer·Tristan A Barnes, Eitan Amir
Dec 23, 2017·Cellular and Molecular Bioengineering·Jutaek NamJames J Moon
Dec 24, 2017·Molecular Immunology·Ralph E Vatner, Edith M Janssen
Feb 28, 2018·Bioconjugate Chemistry·Rui KuaiJames J Moon
May 5, 2018·EBioMedicine·Carole AchardCarolina S Ilkow
May 22, 2018·Frontiers in Immunology·Flávia CastroMaria José Oliveira
Feb 26, 2019·Frontiers in Immunology·Paola BonaventuraStéphane Depil
Aug 14, 2019·Nature Biomedical Engineering·Lindsay ScheetzJames J Moon
Oct 17, 2019·Cancer Immunology, Immunotherapy : CII·A Marijne HeerenEkaterina S Jordanova
May 23, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yong FangShuqing Chen
May 28, 2020·Frontiers in Immunology·Florent PetitprezWolf H Fridman
Jul 2, 2020·Trends in Cancer·Qianqian DuanLianjun Zhang
Jan 22, 2021·Nature Reviews. Clinical Oncology·Eryn Blass, Patrick A Ott

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