Converting Immune Cold into Hot by Biosynthetic Functional Vesicles to Boost Systematic Antitumor Immunity

IScience
Ming WuXiaolong Liu

Abstract

Immune cold tumor characterized by low immunogenicity, insufficient and exhausted tumor-infiltrating lymphocytes, and immunosuppressive microenvironment is the main bottleneck responsible for low patient response rate of immune checkpoint blockade. Here, we developed biosynthetic functional vesicles (BFVs) to convert immune cold into hot through overcoming hypoxia, inducing immunogenic cell death, and immune checkpoint inhibition. The BFVs present PD1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the surface, whereas load catalase into their inner core. The TRAIL can specifically induce immunogenic death of cancer cells to initiate immune response, which is further synergistically strengthened by blocking PD1/PDL1 checkpoint signal through ectogenic PD1 proteins on BFVs. The catalase can produce O2 to overcome tumor hypoxia, in turn to increase infiltration of effector T cells while deplete immunosuppressive cells in tumor. The BFVs elicit robust and systematic antitumor immunity, as demonstrated by significant regression of tumor growth, prevention of abscopal tumors, and excellent inhibition of lung metastasis.

References

Dec 26, 2006·Nature Medicine·Michel ObeidGuido Kroemer
Jan 16, 2010·Cell Death and Differentiation·S P CullenS J Martin
Jan 5, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole JollerVijay K Kuchroo
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Dec 29, 2012·Respiratory Care·Richard H Kallet, Michael A Matthay
Jun 4, 2013·The New England Journal of Medicine·Jedd D WolchokMario Sznol
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Idit Sagiv-BarfiRonald Levy
Apr 22, 2015·The New England Journal of Medicine·Caroline RobertUNKNOWN KEYNOTE-006 investigators
Aug 28, 2015·American Journal of Physiology. Cell Physiology·Muhammad Zaeem NomanSalem Chouaib
Sep 16, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J NaidooJ D Wolchok
Apr 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Theresa L WhitesideIgnacio Melero
Nov 3, 2016·The New England Journal of Medicine·Vassiliki A Boussiotis
Nov 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Xinyi JiangFan Yang
May 26, 2017·Nature Reviews. Cancer·Silvia von KarstedtHenning Walczak
Apr 16, 2018·Advanced Materials·Xudong ZhangZhen Gu
Apr 18, 2018·Therapeutic Advances in Medical Oncology·Eric C Ko, Silvia C Formenti
Apr 25, 2018·Nature Medicine·Mikhail BinnewiesMatthew F Krummel
May 29, 2018·Trends in Immunology·Tae Kon KimLieping Chen
Aug 1, 2018·Nano Letters·Xudong ZhangZhen Gu
Nov 30, 2018·Nature Reviews. Drug Discovery·Jun TangYunqing Lin
Jan 6, 2019·Nature Reviews. Drug Discovery·Jérôme Galon, Daniela Bruni
Aug 30, 2019·Nature Communications·Anna GalstyanJulia Y Ljubimova

❮ Previous
Next ❯

Citations

May 6, 2021·Therapeutic Advances in Gastroenterology·Salomon M ManzMichael Scharl
Jun 15, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Shuangying QiaoJingfeng Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
transmission electron microscopy
dynamic light scattering
pull down
transfection
transmission
immunoprecipitation
ELISA
flow cytometry
FACS
Fluorescence microscopy

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.