Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies

Reynolds, Carson R.; Tran, Son; Jain, Mohit; Narendran, Aru

doi:10.3390/vaccines10020196

Cited by 12 publications

(6 citation statements)

References 124 publications

(251 reference statements)

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“…This method requires the accurate identification and prediction of existing suitable epitopes in individuals, which are then synthesized into peptides or even fulllength proteins to properly trigger an antigen presentation by the patient's HLA repertoire on DCs. 362,364 In several clinical trials, personalized neoantigen peptide-pulsed DCs have been tested against cancers, including melanoma, ovarian cancer, NSCLC and pancreatic cancers. DCs pulsed with synthetic long peptides and adjuvant Poly(I:C) broaden the breadth and diversity of neoantigen-specific T lymphocytes in melanoma.…”

Section: Nucleic Acid Vaccinesmentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

147

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Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

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Section: Nucleic Acid Vaccinesmentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

147

View full text Add to dashboard Cite

show abstract

“…Although neoantigen vaccines have great prospects, the design of such vaccines depends heavily on the continuous optimization of algorithms, including HLA typing, binding strength of neoantigens and MHC, and T cell receptor (TCR) analysis. They are further limited by the median time from screening neoantigens to vaccine preparation of 103 days (ranging from 89 to 160 days), which is too long for patients with advanced tumors who urgently demand individualized treatment 25,251,272–274 . Despite these difficulties, mRNA vaccines targeting tumor neoantigens may enable in a new era of personalized treatment.…”

Section: Mrna Cancer Vaccinesmentioning

confidence: 99%

“…They are further limited by the median time from screening neoantigens to vaccine preparation of 103 days (ranging from 89 to 160 days), which is too long for patients with advanced tumors who urgently demand individualized treatment. 25,251,[272][273][274] Despite these difficulties, mRNA vaccines targeting tumor neoantigens may enable in a new era of personalized treatment.…”

Section: Personalized Neoantigen-encoding Mrna Vaccinesmentioning

confidence: 99%

mRNA vaccines in the prevention and treatment of diseases

Duan

Yang

et al. 2022

MedComm

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Messenger ribonucleic acid (mRNA) vaccines made their successful public debut in the effort against the COVID‐19 outbreak starting in late 2019, although the history of mRNA vaccines can be traced back decades. This review provides an overview to discuss the historical course and present situation of mRNA vaccine development in addition to some basic concepts that underly mRNA vaccines. We discuss the general preparation and manufacturing of mRNA vaccines and also discuss the scientific advances in the in vivo delivery system and evaluate popular approaches (i.e., lipid nanoparticle and protamine) in detail. Next, we highlight the clinical value of mRNA vaccines as potent candidates for therapeutic treatment and discuss clinical progress in the treatment of cancer and coronavirus disease 2019. Data suggest that mRNA vaccines, with several prominent advantages, have achieved encouraging results and increasing attention due to tremendous potential in disease management. Finally, we suggest some potential directions worthy of further investigation and optimization. In addition to basic research, studies that help to facilitate storage and transportation will be indispensable for practical applications.

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“…Создание персонализированных противораковых вакцин сопряжено с рядом проблем, в отличие от других типов вакцин. Важен строгий контроль различных этапов разработки, производства и введения, чтобы обеспечить эффективность и безопасность персонализированных вакцин [23].…”

Section: разработка и производство неопептидных вакцинunclassified

Technological aspects of creating neopeptide vaccines

Дмитриева

Барышникова

Орлова

et al. 2022

Rossijskij bioterapevtičeskij žurnal

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Personalized neoantigen vaccines are a group of individually designed cancer vaccines that enhance patients’ own antigen-specific immune responses. These include vaccines based on dendritic cells, DNA, mRNA and synthetic peptides. An analysis of 98 clinical trials of neoantigenic vaccines from the ClinicalTrials.gov database found that peptide vaccines are one of the most popular cancer vaccines, accounting for about 50 % of clinical trials. They usually consist of a mixture of long or short peptides, dissolved depending on their properties in an appropriate solvent, and an adjuvant that stabilizes and increases their effectiveness. The most used immunoadjuvants in the formulation of neopeptide vaccines are Toll-like receptor agonists (poly-ICLC) and granulocyte-macrophage colony-stimulating factor. The development of neoantigenic vaccines presents a number of distinctive challenges compared to other types of vaccines. The process should cover and validate the various steps in the development, production and administration processes in order to maximize the efficacy and safety of vaccines. In the technology for the production of peptide vaccines, 3 main stages can be distinguished: 1) screening and identification of neoepitopes using the approaches of computer prediction, co-immunoprecipitation, mass spectrometry and cytotoxic experiments; 2) synthesis of peptides by methods of standard solid-phase synthetic peptide chemistry; 3) actually obtaining a vaccine preparation suitable for storage, transportation and administration to the patient. Taking into account the specificity of the drug, the manufacturing process must be carried out strictly according to the Good Manufacturing Practice standard with mandatory quality control of intermediate and finished products

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Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies

Cited by 12 publications

References 124 publications

Neoantigens: promising targets for cancer therapy

Neoantigens: promising targets for cancer therapy

mRNA vaccines in the prevention and treatment of diseases

Technological aspects of creating neopeptide vaccines

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