Expanded Spectrum and Increased Incidence of Adverse Events Linked to COVID-19 Genetic Vaccines: New Concepts on Prophylactic Immuno-Gene Therapy, Iatrogenic Orphan Disease, and Platform-Inherent Challenges DOI Creative Commons
János Szebeni

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 450 - 450

Published: March 31, 2025

The mRNA- and DNA-based “genetic” COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on the timing data analysis methods used. Focusing only lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces evolution statistical conclusions prevalence AEs incidents associated these from initial underestimation atypical, severe toxicities to recent claims suggesting possible contribution vaccinations excess deaths observed in many countries over past few years. Among hundreds different listed Pfizer’s pharmacovigilance survey, present categorizes main symptoms according organ systems, nearly all them being affected. Using US Vaccine Adverse Event Reporting System global vaccination dataset, comparison incidence rates induced by genetic versus flu revealed an average 26-fold increase use vaccines. difference is especially pronounced case ‘Brighton-listed’ AEs, which are also post-COVID conditions. these, increases relative given as x-fold rises, were 1152x, 455x, 226x, 218x, 162x, 152x, 131x for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, hypertension, respectively. delineates concept that be regarded prophylactic immuno-gene therapies chronic disabling might categorized iatrogenic orphan diseases. It examines unique vaccine characteristics could causally related abnormal immune responses potentially lead complications. These new insights may contribute improving safety platform technology assessing risk/benefit balance various products.

Language: Английский

Current and future immunotherapeutic approaches in pancreatic cancer treatment DOI Creative Commons
Pooya Farhangnia, Hossein Khorramdelazad, Hamid Nickho

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 4, 2024

Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.

Language: Английский

Citations

39

Computational biology and artificial intelligence in mRNA vaccine design for cancer immunotherapy DOI Creative Commons
Saber İmani, Xiaoyan Li,

Keyi Chen

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 20, 2025

Messenger RNA (mRNA) vaccines offer an adaptable and scalable platform for cancer immunotherapy, requiring optimal design to elicit a robust targeted immune response. Recent advancements in bioinformatics artificial intelligence (AI) have significantly enhanced the design, prediction, optimization of mRNA vaccines. This paper reviews technologies that streamline vaccine development, from genomic sequencing lipid nanoparticle (LNP) formulation. We discuss how accurate predictions neoantigen structures guide sequences effectively target cells. Furthermore, we examine AI-driven approaches optimize mRNA-LNP formulations, enhancing delivery stability. These technological innovations not only improve but also enhance pharmacokinetics pharmacodynamics, offering promising avenues personalized immunotherapy.

Language: Английский

Citations

10

Clinical advances of mRNA vaccines for cancer immunotherapy DOI Creative Commons
Alexey V. Yaremenko, Muhammad Muzamil Khan,

Xueyan Zhen

et al.

Med, Journal Year: 2025, Volume and Issue: 6(1), P. 100562 - 100562

Published: Jan. 1, 2025

Language: Английский

Citations

8

Leveraging mRNA technology for antigen based immuno-oncology therapies DOI Creative Commons
Charalampos S. Floudas, Siranush Sarkizova, Michele Ceccarelli

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010569 - e010569

Published: Jan. 1, 2025

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system tumor and boost efficacy therapies. Selecting suitable antigens is key step devising vaccinations amplifying response. Tumor neoantigens de novo epitopes derived from somatic mutations, avoiding T-cell central tolerance self-epitopes inducing responses tumors. identification prioritization patient-specific based on advanced computational algorithms taking advantage profiling with next-generation sequencing considering factors involved human leukocyte antigen (HLA)-peptide-T-cell receptor (TCR) complex formation, including peptide presentation, HLA-peptide affinity, TCR recognition. This review discusses development clinical mRNA oncology, particular focus recent trials workflows methodologies for identifying both shared individual antigens. While this centers therapeutic targeting existing tumors, it does not cover preventative vaccines. Preclinical experimental validations crucial vaccine development, but we emphasize approaches that facilitate neoantigen selection design, highlighting their role advancing development. versatility rapid potential make ideal platform personalized immunotherapy. We explore various strategies target identification, tumor-associated tumor-specific tools used predict capable eliciting strong responses. address design considerations enhancing immunogenicity stability vaccines, as well emerging trends challenges field. comprehensive overview highlights mRNA-based underscores ongoing research efforts aimed at optimizing these improved outcomes.

Language: Английский

Citations

4

mRNA vaccine platforms: linking infectious disease prevention and cancer immunotherapy DOI Creative Commons
Dariush Haghmorad, Majid Eslami,

Niloufar Orooji

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: March 12, 2025

The advent of mRNA vaccines, accelerated by the global response to COVID-19 pandemic, marks a transformative shift in vaccine technology. In this article, we discuss development, current applications, and prospects vaccines for both prevention treatment infectious diseases oncology. By leveraging capacity encode antigens within host cells directly, provide versatile scalable platform suitable addressing broad spectrum pathogens tumor-specific antigens. We highlight recent advancements design, innovative delivery mechanisms, ongoing clinical trials, with particular emphasis on their efficacy combating diseases, such as COVID-19, Zika, influenza, well emerging potential cancer immunotherapy. also address critical challenges, including stability, optimization immune responses, broader issue accessibility. Finally, review strategies advancing next-generation aim overcoming limitations technology enhancing preventive therapeutic approaches oncological diseases.

Language: Английский

Citations

2

Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications DOI Creative Commons
Yingying Shi,

Miaoyuan Shi,

Yì Wáng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

Citations

13

Next-generation combination approaches for immune checkpoint therapy DOI
Sangeeta Goswami, Kristen E. Pauken, Linghua Wang

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(12), P. 2186 - 2199

Published: Nov. 25, 2024

Language: Английский

Citations

12

Recent Advances and Prospects in RNA Drug Development DOI Open Access
Hidenori Tani

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12284 - 12284

Published: Nov. 15, 2024

RNA therapeutics have undergone remarkable evolution since their inception in the late 1970s, revolutionizing medicine by offering new possibilities for treating previously intractable diseases. The field encompasses various modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), and messenger (mRNAs), each with unique mechanisms applications. foundation was laid 1978 discovery that synthetic could inhibit viral replication, followed pivotal developments such as interference's 1998. COVID-19 pandemic marked a crucial turning point, demonstrating potential of mRNA vaccines accelerating interest RNA-based approaches. However, significant challenges remain, stability issues, delivery to target tissues, off-target effects, immunogenicity concerns. Recent advancements chemical modifications, systems, integration AI technologies are addressing these challenges. has seen notable successes, approved treatments spinal muscular atrophy hereditary transthyretin-mediated amyloidosis. Looking ahead, show promise personalized approaches, particularly genetic disorders cancer. continued this field, driven technological innovations deeper understanding biology, suggests transformative impact on future medical treatments. purpose review is provide comprehensive overview evolution, current state, prospects therapeutics.

Language: Английский

Citations

9

CLINICAL DEVELOPMENT OF IMMUNO-ONCOLOGY THERAPEUTICS DOI Creative Commons
Jianxin Wang, Qi Chen, Qi Shan

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217616 - 217616

Published: March 1, 2025

Language: Английский

Citations

2

Tetra-branched ionizable lipids enhance the stability and transfection efficiency of lipid nanoparticles for mRNA delivery DOI
Haoran Xu, Jiaqi Fan, Ji‐Wei Liu

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110833 - 110833

Published: Jan. 1, 2025

Language: Английский

Citations

1