A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer
Qianqian Ni,Qianqian Ni,Fuwu Zhang,Yijing Liu,Zhantong Wang,Guocan Yu,Brian Liang,Gang Niu,Ting Su,Guizhi Zhu,Guangming Lu,Longjiang Zhang,Xiaoyuan Chen +12 more
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It is concluded that banNVs are promising to optimize personalized therapeutic neoantigen vaccines for cancer immunotherapy.Abstract:
Neoantigen vaccines have been enthusiastically pursued for personalized cancer immunotherapy while vast majority of neoantigens have no or low immunogenicity. Here, a bi-adjuvant neoantigen nanovaccine (banNV) that codelivered a peptide neoantigen (Adpgk) with two adjuvants [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] was developed for potent cancer immunotherapy. Specifically, banNVs were prepared by a nanotemplated synthesis of concatemer CpG, nanocondensation with cationic polypeptides, and then physical loading with hydrophobic R848 and Adpgk. The immunogenicity of the neoantigen was profoundly potentiated by efficient codelivery of neoantigen and dual synergistic adjuvants, which is accompanied by reduced acute systemic toxicity. BanNVs sensitized immune checkpoint programmed death receptor 1 (PD-1) on T cells, therefore, a combination of banNVs with aPD-1 conspicuously induced the therapy response and led to complete regression of 70% neoantigen-specific tumors without recurrence. We conclude that banNVs are promising to optimize personalized therapeutic neoantigen vaccines for cancer immunotherapy.read more
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Turning cold tumors into hot tumors by improving T-cell infiltration.
Yuan-Tong Liu,Zhi-Jun Sun +1 more
TL;DR: A critical review of the understanding of the mechanisms underlying “cold tumors”, including impaired T- cell priming and deficient T-cell homing to tumor beds is presented, and new possibilities for the development of multiple T cell-based combination therapies to improve ICI effectiveness are discussed.
Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release
Petr O. Ilyinskii,Christopher J. Roy,Conlin O'neil,Erica Browning,Lynnelle Pittet,David H. Altreuter,Frank Alexis,Elena Tonti,Jinjun Shi,Pamela Basto,Matteo Iannacone,Aleksandar F. Radovic-Moreno,Robert Langer,Omid C. Farokhzad,Ulrich H. von Andrian,Lloyd Johnston,Takashi Kei Kishimoto +16 more
TL;DR: It is demonstrated that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines.
Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy
TL;DR: In this paper, a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination was presented. But it remains unclear how to exploit ICD for cancer immunotherapy.
Journal ArticleDOI
Nanomedicine‐Boosting Tumor Immunogenicity for Enhanced Immunotherapy
Jing Huang,Jing Huang,Bin Yang,Yuan Peng,Jinsheng Huang,Siu Hong Dexter Wong,Liming Bian,Kangshun Zhu,Xintao Shuai,Shisong Han,Shisong Han,Shisong Han +11 more
TL;DR: This review highlights how nanomedicines integrating one or more anticancer therapeutic methods to increase the tumor immunogenicity for rousing T cell related immune responses and achieving inspiring antitumor efficacy in synergistic ways.
Journal ArticleDOI
PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake
TL;DR: This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition and involves the combination of checkpoint inhibitors with other agents, enhancing the therapeutic efficacy.
References
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Cancer immunotherapy comes of age
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An immunogenic personal neoantigen vaccine for patients with melanoma
Patrick A. Ott,Zhuting Hu,Derin B. Keskin,Derin B. Keskin,Sachet A. Shukla,Sachet A. Shukla,Jing Sun,David J. Bozym,Wandi Zhang,Adrienne M. Luoma,Anita Giobbie-Hurder,Lauren Peter,Christina Chen,Oriol Olive,Todd A. Carter,Shuqiang Li,David J. Lieb,Thomas Eisenhaure,Evisa Gjini,Jonathan Stevens,William J. Lane,Indu Javeri,Kaliappanadar Nellaiappan,Andres M. Salazar,Heather Daley,Michael S. Seaman,Elizabeth I. Buchbinder,Elizabeth I. Buchbinder,Charles H. Yoon,Maegan Harden,Niall J. Lennon,Stacey Gabriel,Scott J. Rodig,Scott J. Rodig,Dan H. Barouch,Dan H. Barouch,Dan H. Barouch,Jon C. Aster,Jon C. Aster,Gad Getz,Gad Getz,Kai W. Wucherpfennig,Donna Neuberg,Jerome Ritz,Jerome Ritz,Eric S. Lander,Eric S. Lander,Edward F. Fritsch,Edward F. Fritsch,Nir Hacohen,Nir Hacohen,Catherine J. Wu +51 more
TL;DR: The feasibility, safety, and immunogenicity of a vaccine that targets up to 20 predicted personal tumour neoantigens is demonstrated and a strong rationale for further development of this approach, alone and in combination with checkpoint blockade or other immunotherapies is provided.
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Journal ArticleDOI
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
Matthew M. Gubin,Xiuli Zhang,Heiko Schuster,Etienne Caron,Jeffrey P. Ward,Takuro Noguchi,Yulia Ivanova,Jasreet Hundal,Cora D. Arthur,Willem Jan Krebber,Gwenn E. Mulder,Mireille Toebes,Matthew D. Vesely,Samuel S. K. Lam,Alan J. Korman,James P. Allison,Gordon J. Freeman,Arlene H. Sharpe,Erika L. Pearce,Ton N. Schumacher,Ruedi Aebersold,Hans-Georg Rammensee,Cornelis J. M. Melief,Elaine R. Mardis,William E. Gillanders,Maxim N. Artyomov,Robert D. Schreiber +26 more
TL;DR: Tumour-specific mutant proteins are identified as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and it is shown that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy.
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