Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses Against Hepatocellular Carcinoma

Cancers
Leyre SilvaPablo Sarobe

Abstract

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased up...Continue Reading

References

Feb 14, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y WadaM Kojiro
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chie Kudo-SaitoJames W Hodge
May 15, 2010·Journal of Experimental & Clinical Cancer Research : CR·James O'BeirnePhillip M Harrison
Jan 12, 2013·The FEBS Journal·Jorge Filmus, Mariana Capurro
Sep 5, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tobias FleckenRobert Thimme
Jul 9, 2014·Nature Reviews. Clinical Oncology·Ignacio MeleroHåkan Mellstedt
Mar 11, 2015·Nature·Christina Twyman-Saint VictorAndy J Minn
May 16, 2015·Cancer Research·Michele W L TengMark J Smyth
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
May 10, 2016·Nature Reviews. Disease Primers·Josep M LlovetGregory Gores
Jun 30, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Naiyer A RizviScott Antonia
Nov 7, 2016·Journal of Hepatology·Austin G DuffyTim F Greten
Nov 16, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mercedes IñarrairaeguiBruno Sangro
Oct 6, 2018·Oncoimmunology·Maria TagliamonteLuigi Buonaguro
Aug 24, 2019·Nature Reviews. Gastroenterology & Hepatology·Ju Dong YangLewis R Roberts
Dec 1, 2019·Journal for Immunotherapy of Cancer·Jiaqiang MaXiaoming Zhang
May 14, 2020·The New England Journal of Medicine·Richard S FinnUNKNOWN IMbrave150 Investigators
May 30, 2020·Cell Research·Yonina R Murciano-GoroffJedd D Wolchok
Jul 28, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gen-Sheng FengXiaoxue Lin
Jul 28, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Richard S FinnJosep M Llovet

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PMA

Software Mentioned

FlowJo
GraphPad Prism

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.