mRNA vaccine for cancer immunotherapy

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Feb. 25, 2021

Abstract mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. vaccine precedes other conventional platforms due to high potency, safe administration, rapid development potentials, cost-effective manufacturing. However, applications been limited by instability, innate immunogenicity, inefficient vivo delivery. Appropriate structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) formulation methods lipid nanoparticles (LNPs), polymers, peptides, investigated overcome these issues. Tuning the administration routes co-delivery of multiple with immunotherapeutic agents (e.g., checkpoint inhibitors) further boosted host anti-tumor immunity increased likelihood cell eradication. With recent U.S. Food Drug Administration (FDA) approvals LNP-loaded prevention COVID-19 therapeutic outcomes achieved several clinical trials against aggressive solid tumors, we envision advancing immunotherapy near future. This review provides detailed overview progress existing challenges future considerations applying immunotherapies.

Language: Английский

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Enhancing cancer immunotherapy with nanomedicine

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(5), P. 321 - 334

Published: Jan. 31, 2020

Language: Английский

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Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer

Nature, Journal Year: 2023, Volume and Issue: 618(7963), P. 144 - 150

Published: May 10, 2023

Abstract Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients 1 , yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3 . Here a phase I trial adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA–lipoplex nanoparticles, we synthesized mRNA real time from surgically resected PDAC tumours. After surgery, sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), cevumeran (a maximum 20 per patient) and modified version four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan oxaliplatin). The end points included vaccine-induced neoantigen-specific cells by high-threshold assays, 18-month recurrence-free survival oncologic feasibility. We treated 16 with then 15 mFOLFIRINOX. Autogene was within 3 days benchmarked times, tolerable induced de novo high-magnitude 8 out patients, half targeting more than one neoantigen. Using new mathematical strategy to track clones (CloneTrack) functional found vaccine-expanded comprised up 10% all blood cells, re-expanded booster long-lived polyfunctional effector CD8 + cells. At median follow-up, (responders) had longer (not reached) compared without (non-responders; 13.4 months, P = 0.003). Differences the immune fitness did not confound this correlation, as responders non-responders mounted equivalent immunity concurrent unrelated against SARS-CoV-2. Thus, atezolizumab, mFOLFIRINOX induces substantial activity may correlate delayed recurrence.

Language: Английский

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Tools for translation: non-viral materials for therapeutic mRNA delivery

Nature Reviews Materials, Journal Year: 2017, Volume and Issue: 2(10)

Published: Sept. 12, 2017

Language: Английский

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Turning the corner on therapeutic cancer vaccines

npj Vaccines, Journal Year: 2019, Volume and Issue: 4(1)

Published: Feb. 8, 2019

Abstract Recent advances in several areas are rekindling interest and enabling progress the development of therapeutic cancer vaccines. These have been made target selection, vaccine technology, methods for reversing immunosuppressive mechanisms exploited by cancers. Studies testing different tumor antigens revealed properties that yield high versus normal cell specificity adequate immunogenicity to affect clinical efficacy. A few tumor-associated antigens, host proteins abnormally expressed cells, demonstrated serve as good targets immunotherapies, although many do not possess needed or immunogenicity. Neoantigens, which arise from mutated truly cancer-specific can be highly immunogenic, though vast majority unique each patient’s thus require personalized therapies. Lessons previous expeditions teaching us type magnitude immune responses needed, well technologies achieve these responses. For example, we learning approaches elicit potent, balanced, durable CD4 plus CD8 T expansion necessary Exploration interactions between system has elucidated adaptations enable cells suppress evade attack. This led breakthroughs new drugs, and, subsequently, opportunities combine with vaccines dramatically increase patient Here review this recent progress, highlighting key steps bringing promise within reach.

Language: Английский

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