Cheng Xu; Hao Hong; Yonghyun Lee; Kyong Soo Park; Mingjiao Sun; Tianrui Wang; Marisa Aikins; Yao Xu; James J. Moon · 2020 · ACS Nano
Paper
Therapeutic cancer vaccines require robust cellular immunity for the efficient killing of tumor cells, and recent advances in neoantigen discovery may provide safe and promising targets for cancer vaccines. However, elicitation of T cells with strong antitumor efficacy requires intricate multistep processes that have been difficult to attain with traditional vaccination approaches. Here, a multifunctional nanovaccine platform has been developed for direct delivery of neoantigens and adjuvants to lymph nodes (LNs) and highly efficient induction of neoantigen-specific T cell responses. A PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20-30 nm in diameter) is a highly modular and biodegradable platform for facile preparation of neoantigen vaccines within 2 h. RGO-PEG exhibits rapid, efficient (15-20% ID/g), and sustained (up to 72 h) accumulation in LNs, achieving >100-fold improvement in LN-targeted delivery, compared with soluble vaccines. Moreover, RGO-PEG induces intracellular reactive oxygen species in dendritic cells, guiding antigen processing and presentation to T cells. Importantly, a single injection of RGO-PEG vaccine elicits potent neoantigen-specific T cell responses lasting up to 30 days and eradicates established MC-38 colon carcinoma. Further combination with anti-PD-1 therapy achieved great therapeutic improvements against B16F10 melanoma. RGO-PEG may serve a powerful delivery platform for personalized cancer vaccination.
Analysis
This paper presents a novel nanovaccine platform using reduced graphene oxide nanosheets (RGO-PEG) for efficient delivery of neoantigens and adjuvants to lymph nodes, enhancing anti-tumor T cell responses and eradicating established tumors.
Discovery
Ruby Srivastava
Karthick Vasudevan; T Dhanushkumar; Sripad Rama Hebbar; Prasanna Kumar Selvam; Majji Rambabu; K. Anbarasu; Rohini Karunakaran
Dariush Haghmorad; Majid Eslami; Niloufar Orooji; Iryna Halabitska; Iryna Kamyshna; Oleksandr Kamyshnyi; Valentyn Oksenych
Zachary Sethna; Pablo Guasp; Charlotte Reiche; Martina Milighetti; Nicholas Ceglia; Erin Patterson; Jayon Lihm; George C. Payne; Olga Lyudovyk; Luis A. Rojas; Nan Pang; Akihiro Ohmoto; Masataka Amisaki; Abderezak Zebboudj; Zagaa Odgerel; Emmanuel M. Bruno; Siqi Linsey Zhang; C. K. Cheng; Yuval Elhanati; Evelyna Derhovanessian; Luisa Manning; Felicitas Müller; Ina Rhee; Mahesh Yadav; Taha Merghoub; Jedd D. Wolchok; Olca Baştürk; Mithat Gönen; Andrew S. Epstein; Parisa Momtaz; Wungki Park; Ryan Sugarman; Anna M. Varghese; Elizabeth Won; Avni M. Desai; Alice C. Wei; Michael I. D’Angelica; T. Peter Kingham; Kevin C. Soares; William R. Jarnagin; Jeffrey A. Drebin; Eileen M. O’Reilly; Ira Mellman; Uğur Şahin; Özlem Türeci; Benjamin D. Greenbaum; Vinod P. Balachandran
David A. Braun; Giorgia Moranzoni; Vipheaviny Chea; Bradley A. McGregor; Eryn Blass; Chloe Ran Tu; Allison P. Vanasse; Cleo Forman; Juliet Forman; Alexander B. Afeyan; Nicholas Schindler; Yiwen Liu; Shuqiang Li; Jackson Southard; Steven L. Chang; Michelle S. Hirsch; Nicole R. LeBoeuf; Oriol Olive; Ambica Mehndiratta; Haley Greenslade; Keerthi Shetty; Susan Klaeger; Siranush Sarkizova; Christina B. Pedersen; Matthew Mossanen; Isabel Carulli; Anna Tarren; Joseph Duke-Cohan; Alexis A. Howard; J. Bryan Iorgulescu; Bohoon Shim; Jeremy M. Simon; Sabina Signoretti; Jon C. Aster; Liudmila Elagina; Steven A. Carr; Ignaty Leshchiner; Gad Getz; Stacey Gabriel; Nir Hacohen; Lars Rønn Olsen; Giacomo Oliveira; Donna Neuberg; Kenneth J. Livak; Sachet A. Shukla; Edward F. Fritsch; Catherine J. Wu; Derin B. Keskin; Patrick A. Ott; Toni K. Choueiri
Ting Fan; Congcong Xu; Jichuan Wu; Yihua Cai; WuQiang Cao; Haifa Shen; Mingna Zhang; Hanfei Zhu; Jingxian Yang; Zhounan Zhu; Xiaopin Ma; Jiale Ren; Lei Huang; Qianyun Li; Yuying Tang; Bo Yu; Chunxiu Chen; Mingcheng Xu; Qiuhe Wang; Zhuya Xu; Fengjia Chen; Shujing Liang; Zhixian Zhong; Anmbreen Jamroze; Dean G. Tang; Hangwen Li; Chunyan Dong
Source record